12-month Overall Survival Research Articles

Efficacy and safety of regorafenib plus ICIs as second-line treatment in advanced HCC post-frontline treatment failure: A real-world study from a single center.

e16141 Background: Tyrosine kinase inhibitor or bevacizumab (TKI/Bev) combined with immune checkpoint inhibitors (ICIs) currently represent the preferred frontline therapy for patients with Hepatocellular Carcinoma (HCC). Despite this, clinical evidence guiding therapeutic choice for patients unresponsive to this initial immunotherapy regimen remains scarce. This real-world study aimed to assess the efficacy and safety of regorafenib combined with ICIs in patients with HCC who have exhibited disease progress during treatment with TKI/Bev plus ICIs. Methods: This retrospective analysis encompassed a cohort of patients who transitioned to a combined regimen of regorafenib and immune checkpoint inhibitors (ICIs) after the progression of hepatocellular carcinoma (HCC) following treatment with tyrosine kinase inhibitors (TKIs) or a combination of bevacizumab and ICIs, from January 2019 to November 2023. Key efficacy metrics included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The adverse events (AEs) were systematically classified in accordance with the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). Results: A total of 37 patients were included; 56.8% were Child-Pugh A and 43.2% were Child-Pugh B. Treatment regimens prior to regorafenib and ICIs were lenvatinib plus ICIs in 83.8% of patients, sorafenib plus ICIs in three patients, apatinib plus ICIs, donafenib plus ICIs, and bevacizumab plus ICIs each in one patient. The ORR was 27.0% (10/37), and the DCR was 92.0% (28/37) according to mRECIST criteria. The median PFS was 7.8 months (95% CI, 6.0-9.6). The 6-month and 12-month PFS rates was 60.6% (95% CI, 46.4-79.2) and 40.0% (95% CI, 26.0%-61.6%). The median OS post-regorafenib and ICIs was 16.3 months, with 12-month and 24-month OS rates of 67.0% and 49.7%, respectively. The median OS since first-line treatment initiation was 35.8 months, with OS rates of 94.4% and 72.3% at 12-month and 24-month since first-line treatment initiation, respectively. Subgroup analysis indicated no statistical significance in median PFS between patients with lung metastasis and those without lung metastasis [3.9 months (95% CI, 3.0-4.8) vs 7.80 months (95% CI, 6.1-9.5); P=0.178], but there was a trend toward survival benefit in patients without lung metastasis. Grade 3-4 adverse events were reported in 16.22% of the patients, with no treatment-related fatalities. Conclusions: Regorafenib with ICIs is a promising and tolerable second-line treatment for advanced HCC after initial therapy failure.

The efficacy and safety of donafenib-containing regimens as first-line therapy for hepatocellular carcinoma (HCC): A multicenter retrospective study.

e16243 Background: HCC is a common malignant tumor worldwide, safer and more potent treatments are desperately needed to increase the survival rates of HCC patients. Some studies have shown that transcatheter arterial chemoembolization/hepatic arterial infusion chemotherapy (TACE/HAIC) combined with systemic therapies shows potential synergistic effects in patients with HCC, the ZGDH3-III RCT's findings showed that donafenib(D) is highly safe and effective as first-line treatment for uHCC. This study aimed to evaluate the efficacy and safety of donafenib-containing regimens (D+TACE/HAIC, D+TACE/HAIC+ICI, D+ICI, D) as first-line systemic treatments for HCC patients in the real world. Methods: We retrospectively analyzed patient data from January 2022 to December 2023 in seven Chinese institutions with first-line therapeutic regimens based on donafenib. Donafenib-based treatments were administered to eligible patients until the point of disease progression, death, or intolerable toxicity. We examined the progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) per the modified Response Evaluation Criteria in Solid Tumors, and safety (CTCAE5.0). Results: There were 102 patients in this study (Table). The median age was 60 years (IQR: 52, 68) at the data cut-off in January 2024, with 87.3% of the population being male and 78.4% having HBV infection. Most patients received D+TACE/HAIC therapy (59.8%), D+TACE/HAIC+ICI therapy (35.3%), or other treatments. Median PFS and OS not yet been achieved, respectively, the 12-month PFS and OS rates were 87.0% (95%CI: 79.7%-95.0%) and 91.4% (95%CI: 84.9%-98.4%). The ORR was 68.6% and DCR was 88.2%, with complete response in 14 patients, partial response in 56 patients, stable disease in 20 patients, and progressive disease in 12 patients. Among the population, 51 patients (50.0%) had treatment-related adverse events (TRAE) of any grade, and the incidence of grade 3 TRAE was 13.7% (14/102), none of the patients experienced grade 4 or 5 TRAE. Conclusions: These results preliminarily showed that donafenib-containing treatment regimens exhibited encouraging efficacy and favorable safety profile in patients with HCC. [Table: see text]

The efficacy and safety of donafenib combined with transcatheter arterial chemoembolization and anti-PD-1 antibodies as first-line therapy for hepatocellular carcinoma: A retrospective study.

e16178 Background: In Phase III study (ZGDH3), donafenib showed the survival benefit and better safety compared with sorafenib as the first-line treatment for uHCC. Recently, combination therapies have shown favorable results in patients with HCC. Some studies have shown that molecular targeted drugs combined with anti-PD1 antibodies and TACE exhibit improved anti-tumor efficacy compared with monotherapy. This study aimed to evaluate the efficacy and safety of the combination therapy of donafenib,anti-PD-1 antibodies and TACE as first-line treatments for HCC patients in the real world. Methods: This single-center retrospective study involved patients with histopathologically/cytologically or clinically confirmed HCC at Zhejiang Cancer Hospital between July 2021 and June 2023. Eligible patients were treated with donafenib (100 mg po bid) combined with TACE and anti-PD-1 antibodies until the point of disease progression, death, or intolerable toxicity. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) datas of patients were collected and analyzed according to the mRECIST, and the incidence of adverse events (AEs) was evaluated using CTCAE 5.0. Results: There were 34 patients in this study (Table). The median age was 64 years (IQR: 57, 69) at the data cut-off in January 2024, with 94.1% of the population being male and 82.4% having HBV infection. Of these patients, 5(14.7%) were classed as BCLC stage A, 11(32.3%) were classed as BCLC stage B, and 18 (52.9%) were BCLC stage C. The median PFS was 7.9 months (95%CI, 5.6–NA), and median OS was not reached, respectively, the 12-month PFS and OS rates were 46.9% (95%CI: 16.8%-72.5%) and 96.9% (95%CI: 79.8%-99.6%). The ORR and DCR for all patients were 73.5% and 97.1%, respectively, based on both mRECIST (CR 3 [8.8%], PR 22 [64.7%], SD 8 [23.5%]). The surgical conversion rate was 26.5%. Treatment-related adverse events (TRAE) of any grade were observed by 18 patients (52.9%), of which 4 patients (11.8%) had grade 3 TRAE. No grade 4 or 5 TRAE was observed. Conclusions: The study indicated that donafenib combined with TACE and anti PD-1 antibodies exhibited encouraging efficacy and favorable safety profile in patients with HCC. [Table: see text]

Neoadjuvant tislelizumab combined with lenvatinib plus transcatheter arterial chemoembolization in resectable hepatocellular carcinoma with high-risk of recurrence: A prospective, single-arm, phase II trial.

e16242 Background: Currently, more than 55% of liver cancer patients have recurrence within 1 years after radical surgery. However,there is no standard treatment of neoadjuvant therapy for resectable HCC patients. This study aimed to explore the efficacy and safety of the triple therapy [Tislelizumab combined with lenvatinib plus transcatheter arterial chemoembolization (TACE)] as neoadjuvant therapy in patients with resectable HCC with high-risk of recurrence. Methods: This prospective, single-arm, phase II trial (ChiCTR2200059574) enrolled patients with primary resectable HCC who had not received prior anti-tumor therapy. The recurrence rate was predicted to be > 50% according to the risk predictor ( http://www.asapcalculate.top/Cal2_ch.html ) of early recurrence before surgery. TACE will be performed once on Day 1. Tislelizumab (an anti-PD-1 antibody, 200 mg) intravenously once every 3 weeks and lenvatinib (body weight ≥ 60 kg, 12 mg;< 60 kg, 8 mg) orally daily was initiated 3 days after TACE treatment. Surgery was performed after two cycles of neoadjuvant treatment. After 4-6 weeks of surgery, patients continued to receive tislelizumab and lenvatinib for 6 months to 1 year. Primary endpoint was adverse events (AE) and major pathological reactions. Secondary endpoints were objective response rate (ORR) by mRECIST, relapse-free survival (RFS) and overall survival (OS). Results: From April 2022 to August 2023, 19 patients (median age, 55 years) were enrolled, all Child-Pugh A and ECOG PS 0, mostly males (89.5%) and HBV infection (94.7%). According to mRECIST, the ORR was 94.7% (18/19, CR 2, PR 16), and the DCR was 94.7% too (18/19, CR 2, PR 16, SD 0). In 19 patients, 14 patients had received surgical treatment (R0 resection rates were 100%), 12 patients (12/14, 85.7%) achieved major pathological reaction (necrosis≥90%), and 2 patients (2/14, 14.3%) achieved complete pathological response. For those patients who did not undergo surgery, 3 of them refused surgery, and 2 patients lost the chance of surgery because of disease progression and high ICG R-15, respectively. At the end of the last follow-up (January 20, 2024), tumor recurrence was detected in 2 patients after surgery. The 12-month RFS rate and OS rate were 80.2%(95% CI: 40.4%-94.8%)and 94.7%(95% CI: 68.1%-99.2%), respectively. Median RFS and OS were not reached. No grade 3 or above AE were observed. Conclusions: Tislelizumab, lenvatinib, and TACE were safe and showed promising efficacy as a neoadjuvant therapy for resectable HCC with high risk of recurrence. Clinical trial information: ChiCTR2200059574.

Neoadjuvant sintilimab and platinum-doublet chemotherapy followed by transoral robotic surgery for HPV-associated resectable oropharyngeal cancer: Single-arm, phase II trial.

6011 Background: De-escalation treatments for HPV-associated (HPV+) oropharyngeal cancer (OPC) have been well discussed. Meanwhile, the combination of anti-PD-1 therapy and chemotherapy (immunochemotherapy, ICT) and transoral robotic surgery (TORS) shows promising results in OPC, especially in HPV+ ones. This study aims to investigate the efficacy and safety of neoadjuvant ICT and sequential TORS to reduce functional impairments and omit adjuvant radiotherapy for resectable HPV+ OPC. Methods: In the single-arm, phase II trial, patients with resectable HPV+OPC (cT2-4N0-3M0, AJCC 8.0) were recruited and received neoadjuvant sintilimab (200mg), platinum (cisplatin 60mg/m2, or carboplatin AUC=5), and paclitaxel (nab-paclitaxel 260mg/m2, or docetaxel 75mg/m2) every 3 weeks for 2 cycles, followed by radical surgery (with TORS as an option). The primary endpoint was major pathological response (MPR; defined as residual viable tumor of less than or equal to 10%) in the primary lesion. The secondary endpoints include pathologically complete response (pCR) of all resected lesions, objective response rate (ORR) according to RECIST 1.1, disease-free survival (DFS) rate and overall survival (OS) rate at 1 and 3 years, quality of life (QoL) by EORTC QLQ-H&N35 questionnaire. Results: From February 1, 2022 to November 30, 2023, 27 patients were enrolled and received 2 cycles of neoadjuvant ICT. After neoadjuvant therapy, all 27 cases achieved partial response (PR), the ORR was 100%. Among them, 25 patients received radical surgery (per-protocol population), including 21 with TORSs. The pathological evaluation showed 24 patients (96.0%) achieved MPR, and 13 (52.0%) achieved pCR of all samples including primary lesions and resected lymph nodes. Grade 1-2 treatment-related adverse events (TRAE) occurred in 24/27 patients (88.9%). The most common TRAEs included rash (12, 44.4%), alopecia (10, 37.0%), nausea (8, 29.6%) and weakness (8, 29.6%), while only one patient (3.7%) experienced grade 3 TRAEs, including febrile leukopenia, pneumonia and diarrhea. These adverse reactions were manageable and no surgical delay occurred. After the surgery, the majority of patients had active follow-up without any adjuvant treatment (19/25, 76%), while 4 patients received adjuvant anti-PD-1 therapy and only 2 had adjuvant radiotherapy. At an average follow-up time of 8.2 months, the 6-month DFS and OS were both 100%. Furthermore, compared to the baseline, 22 patients (88%) reported similar or improved QoL scores at 3 months after surgeries. Conclusions: Neoadjuvant sintilimab plus platinum-doublet chemotherapy and sequential TORS achieved satisfactory pathological response, favorable functional preservation and tolerable toxicity in patients with resectable HPV+OPC. Further follow-up is warrant to confirm long-term survival benefits. Clinical trial information: ChiCTR2200058650.

Apatinib and camrelizumab plus Intravenous FOLFOX or hepatic arterial infusion chemotherapy with FOLFOX for advanced HCC: A multicenter, prospective, randomized phase III trial.

TPS4193 Background: The combination of anti-angiogenesis and immune checkpoint blockade showed promising outcomes for advanced hepatocellular carcinoma (HCC). Hepatic artery infusion chemotherapy (HAIC) combined with apatinib and camrelizumab could augment treatment efficacy in preliminary study. But HAIC has disadvantages such as technical limitations, expensive cost, impaired liver function and poor patient comfort. Results from our previous phase II trial (NCT05412589) demonstrate that the triplet treatment of Venous Infusional FOLFOX plus camrelizumab and apatinib showed inspiring antitumor activity and acceptable safety for CNLC stage Ⅲ HCC, especially in those with main portal trunk invasion (Vp4). These results encourage us to further compare the efficacy and safety of intravenous FOLFOX with apatinib and camrelizumab versus HAIC-FOLFOX with apatinib and camrelizumab as first-line treatment in advanced HCC. Methods: This multicenter, randomized, open-label, non-inferiority phase 3 study (NCT06172205) will enroll 192 patients. Essential criteria for patient inclusion encompassed: age between 18 and 75 years; a clinical diagnosis conforms to primary hepatocellular carcinoma (HCC); classification with in BCLC stage C; no prior anti-tumor treatment exposure; presence of at least one measurable tumor as per RECIST v1.1; ECOG performance status score of either 0 or 1; and a Child-Pugh A or B. Eligible patients were randomized (1:1) into two groups. Randomization is stratified by the presence of macrovascular invasion or extrahepatic metastasis (yes vs no), and baseline alpha-fetoprotein concentration (<400 ng/mL vs ≥400 ng/mL). There are 2 arms in the study: (1) Arm A: FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2,5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 hours; q3w; up to 6 cycles) intravenously in combination with apatinib (250 mg po qd) and camrelizumab (200 mg iv q3w). (2) Arm B: hepatic arterial infusion FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil q3w; up to 6 cycles), combined with apatinib (250 mg po qd) and camrelizumab (200 mg iv q3w). The primary endpoint is 6-month progression-free survival (PFS) rate according to RECIST v1.1. Secondary outcomes encompass the Objective response rate, Disease control rate, Duration of response, PFS, Overall survival (OS), along with 12-month PFS rate, 6-month and 12-month OS rates. The additional secondary endpoints include assessment of treatment-related adverse events. With the assumption of a median 6-month PFS rate of 85% in the Arm B and 71% in the Arm A (noninferiority margin, 14%), a total of 162 patients were required under a two-sided 5% significance level and 80% power. Allowing a dropout rate of 15%, we aimed to enroll 192 patients. The trial is currently screening eligible patients. Clinical trial information: NCT06172205 .

A novel and selective oral PI3Kα/δ inhibitor, TQ-B3525, in patients with relapsed and/or refractory follicular lymphoma: A phase II, single-arm, open-label study.

7057 Background: TQ-B3525 is a novel and selective oral PI3K α/δ inhibitor. In an earlier Phase I trial, TQ-B3525 achieved outstanding efficacy in subjects with refractory/relapsed follicular lymphoma (R/R FL) (2020 ASCO Abstract #8058). Here, we report the result from a single-arm, open-label, phase II registration study evaluating the safety and efficacy of TQ-B3525 in R/R FL patients. Methods: This phase II study included exploratory stage 1 and confirmatory stage 2. Patients with R/R FL after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until disease progression or intolerable toxicity. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Secondary endpoints were ORR by investigator assessment; the IRC- and investigator-assessed disease control rate (DCR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: Based on results (ORR, 88.0%; DOR, 11.8 months; PFS, 12.0 months) in 25 patients at stage 1, second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received a median of 3 prior lines, with 56.1% refractory to previous therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3%-93.1%), with 28 (34.2%) complete responses. Seven (8.5%) had stable disease for DCR of 95.1%. Median TTR was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. At median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months; estimated 24-month OS rate was 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events occurred in 63 (76.8%) patients, with neutrophil count decreased (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. Conclusions: TQ-B3525 exhibited favorable efficacy and manageable safety profiles, supporting its potential as a valuable treatment modality for heavily pretreated Chinese R/R/ FL patients. Clinical trial information: NCT04324879 . [Table: see text]

Combining nimotuzumab with PD-L1 inhibitors and chemotherapy to treat esophageal cancer: A retrospective study.

e16072 Background: Combining immunotherapy with targeted therapy and/or chemotherapy has been shown to have superior clinical benefits in cancer treatment. The combination of immunotherapy, targeted therapy, and chemotherapy may be an option for esophageal cancer. This study assessed retrospectively the efficacy and safety of nimotuzumab combined with the PD-L 1 inhibitor and chemotherapy in the treatment of patients with esophageal cancer. Methods: All enrolled patients were from the First Affiliated Hospital of Guangdong Pharmaceutical University between September 2021 and August 2023. All patients received intravenous nimotuzumab (200 mg/w) combining with PD-L1 inhibitors (Tirelizumab; Caralizumab; Sintilimab; Pembrolizumab; Nivolumab and Penpulimab, 6 cycles in total) and chemotherapy (albumin paclitaxel 150mg/m2, cisplatin 25mg/m2, for 1-3 days per cycle, for a total of 6 cycles). The primary endpoint was overall survival (OS). Secondary endpoints consisted of the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Efficacy was assessed according to the criteria of RECIST 1.1 and while adverse events (AEs) were graded according to CTCAE 5.0. Following treatment, patients’ general condition, levels of lymphocytes, IL-6, hs-CRP, PCT, CYFRA21, NSE(E), and SCC were monitored regularly. Results: A total of18 patients diagnosed with EC were enrolled in the study. The majority of the patients were male (16/18), 17 (94.4%) patients diagnosed with esophageal squamous cell carcinoma. Lymphatic metastasis occurred in 13 (72.2%) patients and 5 (27.8%) patients experienced distant metastases. Six (33.3%) patients received radical surgery and five (27.8%) patients did not receive systematic antitumor therapy in the past. 17 (94.4%) patients diagnosed with esophageal squamous cell carcinoma (ESCC). No patient achieved complete response (CR) and 6 (33.3%) patients achieved partial response (PR). The ORR and DCR were 33.3% and 83.3%, respectively. The median OS was not achieved, the 12-month OS rate was 84.8%, 24-month OS rate was 74.2%. The median PFS was 7.9 months, the 12- and 24-month PFS rates were 44.0% and 36.7%, respectively. The incidence of Grade ≥ 3 AEs was 43.85%, including anemia (18.8%), lymphopenia (18.8%) and rash (6.3%). Conclusions: This combinational treatment regimen results in a significant improvement in OS compared to the combination of PD-L1 inhibitors and chemotherapy without increased AEs. Compared to other combinations of targeted drugs with PD-L1 inhibitors and chemotherapy, the use of nituzumab significantly prolonged mPFS and increased OS rates at 12 and 24 months.

The feasibility and tolerability of anlotinib plus PD-1 blockades among patients with previously immunotherapy treated advanced esophageal squamous cell carcinoma (ESCC): Update results of a retrospective exploratory study.

e16006 Background: Immunotherapy (ICI) demonstrated promising efficacy for patients with advanced ESCC in both second-line and first-line treatment clinically. Therefore, whether the patients might benefit from the PD-1 blockades-related regimens when they failed after the previous ICI remained to be identified and the feasibility of PD-1 blockades rechallenge in ESCC was warranted to be explored. As a novel oral multi-targeted tyrosine kinase inhibitor (TKI) for tumor angiogenesis and proliferation, anlotinib was an efficacious second-line monotherapy for ESCC in China and the combination of anlotinib plus PD-1 blockades might be a promising strategy for patients with previously ICI treated advanced ESCC. Methods: This multicenter, retrospective study was planned to include 110 patients with previously ICI treated advanced ESCC from 9 hospitals in China who were treated with anlotinib plus PD-1 blockades in clinical practice from July 2018 to November 2022 consecutively. The Outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. Results: At the date of data-cutoff (May 12 2023), 110 eligible patients were available to be analyzed. Characteristics were as follows: median age of 64 years, male/female 74.5%/25.5%, ECOG PS 0/1/2 22.7%/75.5%/1.8%, clinical stage II/III/IV 0.9%/20.9%/78.2%. All the patients had received ICIs and 10.9% patients were treated with TKIs previously. 39.1% patients had received first-line therapy, 41.8% patients had received second-line, 19.1% patients had received third or above line previously. Prognostic outcomes exhibited that the median OS was 11.1 months (95%CI: 8.6-13.7), 12-month OS rate, 24-month OS rate were 47.6% and 30.8%, separately. Additionally, the median PFS was 5.6 months (95%CI: 4.4-6.8). In 110 patients, ORR was 19.1% (95%CI: 12.2%-27.7%), DCR 69.1% (95%CI: 59.6%-77.6%). Safety profile of anlotinib plus PD-1 blockades indicated that the treatment related adverse events (TRAEs) were 89.1%. The most common TRAEs were anaemia (62.7%), hypothyroidism (25.5%), hypoalbuminemia (21.8%), lymphocytopenia (20%), leukopenia (19.1%). Conclusions: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and tolerable adverse reactions among patients with advanced ESCC who had received immunotherapy previously and the feasibility of PD-1 blockades rechallenge in ESCC was promising to be elucidated. Clinical trial information: ChiCTR2300070777.

Recent safety and efficacy findings from a phase 1b/2 open-label combination study of ASP-1929 photoimmunotherapy with anti-PD-1 therapy in EGFR-expressing advanced head and neck squamous cell carcinoma (HNSCC).

6083 Background: In the challenging landscape of advanced HNSCC, patients (pts) have overall low survival and high locoregional (LR) recurrence rates. While LR progression is a key contributor to morbidity and mortality, LR control remains low despite aggressive therapy including surgery, radiation, chemotherapy, and immunotherapy. ASP-1929 photoimmunotherapy (PIT) combines EGFR-targeting cetuximab, with a light-activatable dye, IRDye 700DX, and a laser light for localized drug activation. This novel approach has demonstrated rapid and selective tumor necrosis in preclinical studies, and a manageable safety profile in HNSCC early clinical trials. Phase I/II and preclinical data indicate a potential synergy in anti-tumor activity of PIT when combined with anti-PD-1 therapy. Here we present updated interim evaluation findings based on a recent data cut from this study initially presented at the 2023 American Head and Neck Society meeting. Methods: A phase 1b/2 open-label study of pts with recurrent locally advanced (rLA) and/or metastatic (m) HNSCC evaluating the safety and efficacy of ASP-1929 PIT in combination with anti-PD-1 (pembrolizumab) therapy (NCT04305795). Pts with measurable disease by modified RECIST 1.1, at least 1 lesion accessible to light illumination, combined positive score (CPS) ≥1, and who were not candidate for LR therapy could be eligible for the study. Treatment included ASP-1929 PIT (infusion day 8, target tumors illuminated 24±4 hours later) plus anti-PD-1 (days 1&22) during a 6-week cycle for up to 24 months. Primary objectives: safety/tolerability; objective response rate (ORR). Secondary objectives: overall survival (OS); progression-free survival (PFS); duration of response (DOR). Planned sample size: 26 HNSCC pts. Results: Of the 19 r/m HNSCC pts enrolled, 18 pts received both study therapies (PIT-evaluable). Data cut-off was August 31, 2023 (previously reported data cut-off: October 4, 2022). Efficacy results updated for the 18 PIT-evaluable pts: ORR of 33.3% (95% CI 13.3-59.0), including 4 CRs (22.2%) and 2 PRs (11.1%). Median OS not reached; 24-month OS rate estimate was 52.4% (95%CI 25.9-73.4). No change in median PFS, 2.9 months (95%CI 1.4-14.6). Median DOR was not reached at data cut-off (range 2.8+ to 18.0+ months). Safety data remained consistent with the data previously presented. Most common serious adverse reactions were dysphagia (10.5%) and tongue edema (10.5%). There were two grade 4 events: laryngeal edema (PIT-related) and tumor hemorrhage due to advanced disease, and no fatal events. Conclusions: ASP-1929 PIT in combination with anti-PD-1 therapy was generally well tolerated. Initial data demonstrate promising overall survival and response rates with this combination therapy in pts with rLA and/or m HNSCC lacking LR treatment options. Clinical trial information: NCT04305795 .

A phase 1/2 study of favezelimab in combination with pembrolizumab for anti–PD-1–naive relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL): An updated analysis.

7055 Background: PD-1 inhibitors such as pembrolizumab are an important treatment option for patients (pts) with R/R cHL, but treatment failure remains a significant challenge. Dual immune checkpoint blockade with a PD-1 inhibitor and a lymphocyte-activation gene 3 (LAG-3) inhibitor shows promise as a treatment option for R/R cHL. In a multicohort phase 1/2 study (NCT03598608) evaluating the anti–LAG-3 monoclonal antibody favezelimab in combination with pembrolizumab for R/R hematologic malignancies, pembrolizumab plus favezelimab demonstrated sustained antitumor activity and acceptable safety in the cohort of pts with anti–PD-1–naive R/R cHL (cohort 1). We present updated results from this cohort after additional follow-up. Methods: Eligible pts were aged ≥18 years with R/R cHL; prior treatment with or ineligibility for autologous stem cell transplantation or no response to salvage chemotherapy; no prior PD-1 inhibitor; and an ECOG PS of 0 or 1. The study comprised a safety lead-in (pembrolizumab 200 mg IV Q3W plus favezelimab 200-mg starting dose, then dose escalation to 800 mg IV Q3W using a modified toxicity probability interval method) and a dose expansion phase (pembrolizumab 200 mg Q3W plus favezelimab at the established recommended phase 2 dose of 800 mg Q3W for up to 35 cycles). Primary end point was safety. Objective response rate (ORR) per IWG 2007 criteria by investigator review was a secondary end point. Duration of response (DOR) and progression-free survival (PFS) per IWG 2007 criteria by investigator review and overall survival (OS) were exploratory. Results: Cohort 1 enrolled 30 pts. The median time from first dose to data cutoff (August 15, 2023) was 36.9 months (range, 29.4-48.6). Treatment-related adverse events (AEs) occurred in 27 pts (90%), of which the most common (≥20%) were hypothyroidism (27%), infusion-related reaction (23%), and fatigue (20%). Grade 3 or 4 treatment-related AEs occurred in 7 pts (23%). Five pts (17%) discontinued treatment due to treatment-related AEs. No deaths due to treatment-related AEs were reported. AEs of clinical interest occurred in 20 pts (67%); 3 pts (10%) had grade 3 events (colitis, pneumonitis, severe skin reaction) and 1 pt (3%) had a grade 4 event (hepatitis). The ORR was 83% (n = 25; 95% CI, 65-94); 11 pts (37%) had a complete response and 14 (47%) had a partial response. Median DOR was 17.0 months (range, 2.6-30.5), and an estimated 47% of responders remained in response at 24 months. Median PFS was 19.4 months (95% CI, 9.5-28.5), and the 24-month PFS rate was 46%. Median OS was not reached (NR; 95% CI, NR-NR), and the 24-month OS rate was 93%. Conclusions: With additional follow-up, favezelimab plus pembrolizumab continued to demonstrate sustained antitumor activity and manageable safety in pts with anti–PD-1–naive R/R cHL. Further studies to investigate this combination are warranted. Clinical trial information: NCT03598608 .

Multimodal fully automated predictive model for therapeutic efficacy of first-line cancer immunotherapy based on clinical information and imaging modalities including brain MRI and chest CT images in advanced non-small cell lung cancer.

1555 Background: The integration of imaging and clinical data through artificial intelligence (AI) holds promise for more accurately predicting the therapeutic efficacy of immune checkpoint inhibitors (ICI) ± platinum-based chemotherapy in individual patients with advanced non-small cell lung cancer (NSCLC). However, tumor segmentation still relies entirely on radiologist evaluation and has not yet achieved fully automated tumor evaluation for image analysis. Furthermore, while central nervous system (CNS) metastasis is a critical prognostic factor in patients with advanced NSCLC, radiomics has primarily focused on chest imaging, with few studies incorporating brain MRI analysis. Methods: This study included patients with advanced NSCLC treated with ICI ± platinum-based chemotherapy as first-line therapy from March 2017 to August 2023. We developed an ensemble model combining a logistic regression model that analyzes clinical information with a deep learning model that extracts image features. Each sub-model was independent, allowing for individual adjustments and the ability to be attached or detached. Both models were trained to predict response, 12-month progression-free survival (PFS), and 12-month overall survival (OS) using cross-entropy loss. The dataset was randomly divided into training, validation, and test sets in a 5:3:2 ratio. This random assignment was repeated four times, and the average area under the curve (AUC) was calculated. The test sets were further classified into high- and low-risk groups based on the predicted results, and log-rank tests were performed on their survival curves. Results: The study included 232 patients, with 89 (38%) receiving ICI alone and 143 (62%) receiving ICI + platinum-based chemotherapy. In the entire population, the overall response rate (ORR) for ICI ± platinum-based chemotherapy was 49.5%, with a median PFS of 7.1 months (95% confidence interval [CI]: 5.8-9.1) and a median OS of 24.5 months (95% CI: 21.2-30.3). The model achieved an AUC of 0.70 (95% CI: 0.65- 0.76) for predicting response, 0.65 (95% CI: 0.59-0.71) for 12-month PFS, and 0.69 (95% CI: 0.48-0.90) for 12-month OS. Test sets were classified into high-risk (N = 55) and low-risk (N = 60) groups. The median PFS was 6.8 months in the high-risk group and 14.7 months in the low-risk group (p < 0.05). The median OS was 21.5 months in the high-risk group and 34.3 months in the low-risk group (p < 0.05). Conclusions: We have demonstrated that a multimodal, fully automated ensemble model has significant predictive accuracy for the efficacy and survival outcomes of ICI ± platinum-based chemotherapy in patients with advanced NSCLC.

A phase II study of tunlametinib in combination with vemurafenib in patients with BRAF V600-mutant advanced melanoma.

e21519 Background: The new MEK inhibitor tunlametinib combined with the BRAF inhibitor vemurafenib showed promising clinical activity in patients (pts) with BRAF V600-mutant solid tumors in a previous Phase I study (NCT03976050). Based on the result, we designed a phase IIa study to evaluate the efficacy and safety of tunlametinib plus vemurafenib in Chinese pts with BRAF V600 mutant melanoma. Methods: This open-label, single arm, multiple-center phase IIa study enrolled Chinese pts with BRAF V600E-mutant advanced melanoma, without restriction on the disease subtype (e.g., acral, mucosal, or cutaneous melanoma). Prior treatment was permitted, excluding BRAF/MEK inhibitors. Pts received oral tunlametinib at a dose of 9 mg twice daily and vemurafenib 720 mg twice daily. The primary endpoint was the objective response rate (ORR) per RECIST v1.1. Results: Between October 15, 2021, and June 22nd, 2022, 17 pts were enrolled and included in the analysis. Thirteen (76.5%) pts had received previous systemic antitumor therapy, with 12 (70.6%) receiving immunotherapy. Seven (41.2%) pts had acral melanoma, 8 (47.1%) pts had skin melanoma (non-acral) and 2 (11.8%) pts had mucosal melanoma. All pts had metastatic disease. With a median follow-up of 15.3 months (95%CI: 6.8; NE), 12 (70.6%) pts achieved confirmed partial response (PR), resulting in a confirmed ORR of 70.6% (95% CI: 44.0%-89.7%). The disease control rate was 100% (95% CI: 80.5%, 100.0%). The median progression-free survival (PFS) was 10.0 months (95% CI: 5. 5, NE). the duration of response (DOR) was 20.1 (95% CI: 4.2, NE). The overall survival (OS) was 21.6 months (95% CI: 14.5, NE), with a 12-months OS rate of 87.4% (95% CI: 58.1%, 96.7%). Subgroup analysis revealed that in pre-treated pts, the confirmed ORR was 76.9% (95% CI: 46.2%, 95.0%), the median PFS was 10.0 months (95% CI: 5.5, NE), while in previous untreated pts, the mPFS was 14.0 months (95% CI: 9.9, NE). In pts with skin melanoma, the confirmed ORR was 87.5% (47.3%, 99.7%), the mPFS was 10.0 months (95% CI: 5.5, NE), the mOS was 21.6 months (95% CI: 5.7, NE). In pts with acral melanoma, the ORR was 57.1% (95% CI: 18.4%,90.1%), the mPFS was 18.1 months (95% CI: 2.8, NE), the mOS not reached (12.3, NE). The most common adverse events included rash, pyrexia, and elevated blood creatin phosphokinase, most of which were of grade 1-2 severity. Grade 3 or higher TRAEs occurred in 12 (70.6%) pts, of which 41.2% were rash. Most AEs were manageable with supportive therapy or dose interruption. No treatment-related deaths were reported. Conclusions: The addition of a MEK inhibitor tunlametinib to vemurafenibexhibited promising clinical efficacy in Chinese patients with BRAF V600-mutant advanced melanoma, with a manageable safety profile. Additionally, notable effects were observed in pts with acral melanoma. The efficacy in pre-treated patients was comparable to that of similar agents in previous untreated patients. Clinical trial information: NCT05263453 .

The activity and safety of icaritin for patients with unresectable HCC: A real world, retrospective study.

e16181 Background: Primary liver cancer is a major health burden globally, ranking sixth in incidence and third in mortality among all cancers[1]. Over the past 5 years, immune checkpoint inhibitors (ICIs) and multi-targeted tyrosine-kinase inhibitors have emerged as new treatment options for advanced hepatocellular carcinoma[2–4]. Nevertheless, only a small subset of patients with hepatocellular carcinoma derive a response to ICI monotherapy. Icaritin, a target tumor micro-environment(TME) modulating compound, which interacts with MyD88/IkB kinase-a (IKK)[5], inhibiting the TNF-a-induced IKK and nuclear factor-κB (NF-kB) signaling pathways and blocking PD-L1 expression in HBV-related HCC[6-9] and has been approved in China for the treatment of first-line advanced HCC. Icaritin phase III study previously reported at 2021 ASCO, we therefore investigated the efficacy of icaritin in patients with unresectable stage IIA-IIIB (CNLC stage) HCC in a real-world setting. Methods: This multi-center, retrospective study, conducted between May 2022 and Nov 2023. We retrospectively collected medical records of patients (pts) with unresectable IIA-IIIB (CNLC stage) HCC who received icaritin monotherapy (mono-group) or icaritin combined with PD-1/L1 and/or anti-VEGF therapy (combination group) as first line therapy. The primary endpoints were progression free survival (PFS); Secondary endpoints included overall survival (OS) rate, objective response rate (ORR) by RECIST v1.1, and safety. Results: Patients characteristics: 49 pts were eligible for inclusion with median age of 60.7 years old (range 18.0-89.0), 91.8% were ECOG PS 0-1, 86.5% had HBV infection, 79.6% were stage III and 48.9% were AFP>400 ng/ml. 33 pts administrated with combination therapy, other 16 pts’ regimen was icaritin monotherapy. Efficacy: As of the data cutoff for the preliminary analysis of progression free survival (Nov 30, 2023), the median follow-up was 11.17 months (95%CI 6.74–12.12). The ORR for the combination group was 6.06%, and 12.50% for the mono-group, the mPFS was 8.94(95%CI 6.90~9.76) and 5.52 (2.92~NE) for each group. The mOS was not reached for both group, the 6 and 12-months OS rates were 91.00% and 73.67% respectively. Safety: For the safety information, most of TRAEs were grade 1 or 2. No serious AEs were observed. Conclusions: This real-world retrospective study revealed that icaritin monotherapy and icaritin-based combination therapy are promising therapeutic options for unresectable HCC in China. Clinical trial information: ChiCTR2300074565.

A retrospective study on the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) and with/without immunotherapy in intermediate-advanced hepatocellular carcinoma (HCC).

e16171 Background: Recent phase III clinical trial ZGDH3 and several real-world studies have demonstrated the potential of Donafenib in improving overall survival (OS) in advanced HCC. This study aims to evaluate the efficacy and safety of Donafenib combined with TACE and with/without immunotherapy as first-line treatment in intermediate-advanced HCC. By retrospectively analyzing data from previous clinical trials, we will further explore the potential of Donafenib in enhancing the survival rate of patients with intermediate-advanced HCC and its safety profile. Methods: Thirty-eight patients diagnosed with intermediate-advanced HCC through pathology or clinical assessment were included in the study. We conducted a retrospective analysis of the efficacy and safety of patients treated with at least one cycle of Donafenib between September 2021 and December 2023, at the Affiliated Hospital of Nantong University and the Third People's Hospital of Nantong City. The primary endpoints were Objective Response Rate (ORR) and Progression-Free Survival (PFS). Secondary endpoints included Disease Control Rate (DCR), overall survival (OS) and safety. Safety and efficacy were assessed according to CTCAE v5.0 and mRECIST, respectively. Survival data were calculated using the Kaplan-Meier method. Results: The median age was 67 years old, and 76.3% were male. 39.5% of patients had Child-Pugh score A, 39.5% had BCLC stage B, and 60.5% had stage C. 17 patients (44.7%) received Donafenib combined with TACE treatment, while the remaining patients (55.3%) received Donafenib combined with TACE and immunotherapy. The median duration of therapy (mDOT) was 7.18 months (range, 2.14 -21.75). The ORR and DCR were 57.89% (22/38) and 89.47% (34/38), respectively. The median follow-up time was 9.17 months (range, 2.99-27.93), and the 6-month PFS rate was 81.1% (95% CI: 67.1%-98.0%). The 12-month PFS rate was 73.7% (95% CI: 56.5%-96.2%). The 6-month OS rate was 94.0% (95% CI: 86.2%-100.0%), and the 12-month OS rate was 88.1% (95% CI: 75.6%-100.0%), with the median PFS and OS not reached yet. Most patients took Donafenib 200mg twice a day. A total of 6 patients (15.79%) experienced grade 3 adverse events (AEs). The common grade 3 AEs included hand-foot syndrome (7.89%), diarrhea (2.63%), rash (2.63%), and hypertension fatigue (2.63%). No grade 4 or 5 AEs or new safety signals were found. Conclusions: Donafenib combined with TACE and with/without immunotherapy showed manageable safety and promising efficacy in intermediate-advanced HCC patients.

Stereotactic body radiation therapy combined with atezolizumab and bevacizumab for hepatocellular carcinoma with extrahepatic metastasis: Preliminary result of a single-arm study.

e16205 Background: IMbrave150 study confirmed the clinical benefit of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma (HCC). However, patients with extrahepatic metastasis (EHS) had a poorer prognosis. Studies suggested “abscopal effect” of synchronous radiotherapy and immunotherapy may improve antitumor activity. This study aimed to evaluate efficacy and safety of stereotactic body radiation therapy (SBRT) combined with atezolizumab and bevacizumab in HCC patients with EHS. Methods: This single-arm study included HCC patients with EHS from January 2022 to November 2023 in Fudan University Shanghai Cancer Center. Prior tyrosine kinase inhibitor and/or immune checkpoint inhibitor treatment were eligible. After first dose atezolizumab and bevacizumab, SBRT was performed with a total dose of 25-50 Gy. The primary endpoint was objective response rate (ORR). The secondary endpoints included overall survival (OS), disease control rate (DCR), progression-free survival (PFS), time to progression (TTP), and duration of response (DOR). Results: Thirty-nine patients were included. Fourteen patients were treated as first-line therapy and 25 patients were treated as later-line therapy. The mean age was 56.69±11.21 years and 89.7% were male. Of these patients, 66.7% had hepatitis viral infection and 25.6% had vascular invasion. 53.8% of patients had ≥2 extrahepatic spread lesions. In addition, 33.3% of patients had received prior immunotherapy and 23.1% of patients had received tyrosine kinase inhibitor therapy. The median follow-up was 6.50 (range: 1.43-22.17) months. The ORR and DCR were 43.6% and 92.3%, respectively. The ORR was 57.1% and 36.0% in first-line subgroup and later-line subgroup, respectively. The 12-month OS rates was 54.7%. The median PFS, median TTP and median DOR were 6.73 months, 8.67 months, and 7.17 months, respectively. The incidence of all grade TRAE and grade ≥3 TRAE were 38.5% and 12.8%, respectively. The most common grade ≥3 TRAEs were decreased platelet count (7.7%), decreased white blood cell count (2.6%), pruritus (2.6%) and rectal bleeding (2.6%). No serious adverse events occurred. Conclusions: SBRT combined with systemic atezolizumab and bevacizumab showed encouraging efficacy with manageable safety profile for HCC patients with EHS regardless of prior treatment. Further studies are warranted. Clinical trial information: NCT05396937 . [Table: see text]

Efficacy and safety of regorafenib combined with PD-1 inhibitors in patients with advanced hepatocellular beyond atezolizumab plus bevacizumab: A retrospective analysis of real-world evidence.

e16172 Background: In patients with advanced hepatocellular carcinoma (HCC) progressing after atezolizumab and bevacizumab, the optimal therapy scheme is debatable and the efficacy of regorafenib combined with PD-1 inhibitors is still unclear. Methods: In this retrospective study, advanced HCC patients who received regorafenib combined with PD-1 inhibitors progressing after atezolizumab plus bevacizumab were consecutively enrolled from February 2022 to January 2024. Main efficacy endpoint was overall survival (OS), following progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: A total of 11 eligible patients were enrolled, with 8 in Child-Pugh A and 3 in Child-Pugh B7. All patients had hepatitis B infection by with tumor embolus. All patients were classified as Barcelona Clinic Liver Cancer stage C. The AFP level is above 400ng/ml in all patients. At data cut-off at February 2024, the median OS was 16.9 months and the median PFS was 3.7 months. The 3-month and 6-month PFS rates were 70% and 35% , respectively. The 12-month OS rate was 71.4%. Grade≥3 TRAEs occurred in 9.1% (1/11) of the patients. Conclusions: Though application of regorafenib combined with PD-1 inhibitors progressing after atezolizumab plus bevacizumab present safe and effective in our cohort, these data need to be confirmed in prospective comparative studies. [Table: see text]

Efficacy and safety of donafenib combined with anti-PD-1 antibodies for initially unresectable hepatocellular carcinoma (HCC): A retrospective real-world study.

e16131 Background: Given its clear efficacy and high safety demonstrated in the phase 3 ZGDH3 study, donafenib has been recommended by the Chinese guidelines for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). Recently, combination therapies have shown favorable results. However, the clinical experience of donafenib combined with anti-PD-1 therapy for uHCC has not yet been investigated. Thus, we aimed to investigate the efficacy and safety of donafenib combined with anti-PD-1 antibody in the treatment of uHCC. Methods: A single-center, retrospective study was performed based on the medical records of consecutive patients diagnosed with HCC who were not suitable for curative surgery at Hunan Provincial People's Hospital from July 2021 to September 2023. Patient with ≥18 years, no prior systemic therapy, having at least one measurable lesion (per mRECIST) were enrolled. Patients were treated with donafenib and anti-PD-1 antibodies until disease progression or unacceptable toxicity, local treatment such as TACE, HAIC or ablation were allowed. The primary endpoint was progression-free survival (PFS) by mRecist criteria, and secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by mRecist criteria, and safety. The last follow-up time was December 15, 2023. Results: In total, 48 patients were enrolled: 87.5% males, median age 59.5 years (range, 32.0-78.0), 95.8% ECOG of 0, 68.8% HBV positive, 14.6% BCLC stage B, 75.0% BCLC stage C, 47.9% baseline AFP≥400 ng/mL, 70.8% with macrovascular invasion. Among them, 9 patients (18.8%) received donafenib combined with anti-PD-1 antibody as first-line treatment, 37 (77.1%) with concurrent TACE(n = 25) or HAIC(n = 6) or both as treatment(n = 6), 2 (4.2%) received ablation treatment. At the time of data cut-off, the median follow-up time was 10.0 months (95% CI, 6.37-12.2). Considering efficacy, 9 pts (18.7%) achieved complete response, 20 (41.7%) achieved partial response, 17 (35.4%) had stable disease, and 2(4.2%) had progressive disease. The ORR and DCR were 60.4% and 95.8% by mRecist, respectively. Median progression-free survival was 15.8 months (95% CI, 8.9-NA). Median overall survival was not reached, 12-month OS rate were 90.7% (95% CI:73.7%-96.9%). In terms of safety, 44 pts (91.7%) had TRAEs. The incidence of ≥grade 3 TRAEs was 33.3% (16/48). Common TRAEs included elevated AST(45.8%), hand-foot syndrome (39.6%), decreased platelet count(35.4%),elevated ALT(31.2%), rash (25.0%) and decreased white blood cell count (14.6%). Grade 3/4 TRAEs included elevated AST(10.4%), elevated ALT(8.3%), rash(8.3%) and hand-foot syndrome (8.3%). No grade 5 TRAEs were observed. Conclusions: Donafenib combined with anti-PD-1 antibodies shows promising efficacy and manageable toxicity in patients with initially uHCC.

Lung-MAP S1800D: A phase II/III study of N-803 (ALT-803) plus pembrolizumab versus standard of care in participants with stage IV or recurrent non-small cell lung cancer (NSCLC) previously treated with anti-PD-1 or anti-PD-L1 therapy.

2619 Background: IL-15 is a member of the IL-2 common gamma chain family of cytokines. N-803 is IL-15 administered in complex with IL-15 receptor alpha. Lung cancer, despite advances in targeted therapies and immunotherapy, remains the leading cause of cancer related death in the United States. Strategies to improve the performance of immunotherapy in advanced NSCLC is a clinical unmet need. Methods: Lung-MAP S1800D was a randomized study comparing N-803 plus pembrolizumab (NP) to investigators’ choice standard-of-care chemotherapy (SoC) for previously treated advanced NSCLC. Patients were enrolled into an Acquired Resistance Cohort (ARC) if disease progression on prior anti-PD-(L)1 occurred > 84 days from start of treatment and otherwise into a Primary Resistance Cohort (PRC). The ARC was a phase II/III study with a sample size goal of 334 patients. The PRC was a phase II with sample size of 134 patients. The first interim analysis (IA1) in the ARC evaluated futility among the first 25 patients treated with NP which required ≥1 response and ≥50% with disease control at 12 weeks to continue accrual. The primary endpoint in both cohorts was overall survival (OS). Secondary endpoints were progression-free survival (PFS), response, and toxicity. Results: Accrual in the ARC and PRC were closed at the IA1 in the ARC with 74 pts in the ARC and 8 in the PRC. Of the 74 ARC patients, 71 met eligibility (36 SoC, 35 NP), and 32 pts on each arm received treatment. With 44 events, OS was not significantly different between the two arms (HR (95%CI: 0.73(0.40-1.36), p=0.32) with a 12-month OS rate of 25% with SoC and 44% with NP. With 61 events, PFS was not significantly different but numerically worse (HR (95% CI): 1.29 (0.78-2.13, 95% CI), p=0.33). There were 3 unconfirmed partial responses and 1 confirmed complete response with NP and 3 unconfirmed partial responses and 2 confirmed partial responses with SoC. On the NP arm, there were 10 Grade 3 (1 hematologic) and 1 Grade 5 treatment-related adverse events reported as Disease Progression (34% Grade 3+ TRAE). The Grade 3+ TRAE rate on the SoC arm was 53% with 10 Grade 3+ hematologic toxicities. Conclusions: While the study failed to continue accrual past IA1, there is an indication of a subgroup that might benefit from NP with a potential OS difference at 12 months. NP was safe when compared to SoC, and responses were seen in both treatment arms, including partial and complete responses in the NP group. Evaluation of tumor and patient characteristics will be critical to define if there are those who may benefit from N-803 plus pembrolizumab. Clinical trial information: NCT05096663 .

TACE-HAIC combined with donafenib and immunotherapy for hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT): A retrospective analysis.

e16174 Background: The probability of Chinese hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) is relatively large and the long-term survival of this part of patients is poor. Systemic therapy, transcatheter arterial chemoembolization (TACE), and hepatic artery infusion chemotherapy are widely used in HCC patients with PVTT. We want to explore the efficacy and safety of TACE plus hepatic arterial infusion chemotherapy combined with Donafenib, anti-PD-1 antibody in uHCC patients with PVTT. Methods: We retrospectively analyzed the patients who were diagnosed as uHCC with PVTT and received the treatment of TACE plus HAIC combined with Donafenib, anti-PD-1 antibody as first-line therapy from Dec 2021 to Jun 2023 in Harbin Medical University Cancer Hospital. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progress free survival (PFS), overall survival (OS) and safety. Results: Of 106 patients included in the analysis, all of them received first-line treatment of TACE (embolization of pirarubicin hydrochloride 40mg, iodized oil 10-20ml with or without gelatin sponge) plus HAIC (oxaliplatin 85 mg/m2 2h, leucovorin 400 mg/m2 1h, fluorouracil bolus 400 mg/m2 in the first 10 minutes, and fluorouracil infusion 2400 mg/m2 for 46h) combined with donafenib 200mg bid, anti-PD-1 antibody Q3W. The median age was 58 years (IQR, 52-64). The study population was predominantly male (79.2%), and 79.2% were HBV-positive. All HCC patients are accompanied by PVTT, most of which are VP3(72.6%).The rate of patients with extrahepatic metastasis were 16.0%. All patients were classified as BCLC stage C and 84.0% were classified as CNLC stage IIIa. As of December 2023, 106 patients had received at least one imaging evaluation, 11 (10.4%), 60 (56.6%) and 28 (26.4%) of them achieved complete response, partial response and stable disease, and the overall objective response rate and disease control rate was 67.0% and 93.4% per modified RECIST criteria respectively. With 16.3 months of median follow-up time, the 12-month PFS rate was 81.3% and the 12-month OS rate was 90.1%. The median PFS and OS were not reached. 103 of all patients had at least one treatment-related AE (TRAE), and treatment-related deaths did not occur in this study. Grade 3 TRAEs occurred in 33 (31.1%) patients, and no grades 4 or 5 were reported. The most common Grade 3 TRAEs included aspartate transaminase increased (18.9%), platelet count decreased (14.2%) and blood bilirubin increased (8.5%). Conclusions: TACE-HAIC combined with Donafenib and immunotherapy are effective and tolerable for uHCC patients with PVTT.