157P Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) treatment in Chinese patients with unresectable/advanced hepatocellular carcinoma (HCC): CheckMate 9DW expanded analyses

e16191 Background: CS1003 is a novel humanized, recombinant IgG4 anti-PD-1 monoclonal antibody. LEN, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRα, RET, and KIT, is approved as 1L treatment in pts with uHCC in multiple countries. A multi-regional, double-blinded, randomized phase 3 trial (CS1003-305, NCT04194775) of CS1003/placebo in combination with LEN as 1L treatment in uHCC is underway. The preliminary efficacy and safety data from the open-label phase 1b study of CS1003 + LEN as 1L treatment in uHCC after a median 6.2 months of follow-up were previously reported at ESMO Congress 2020. Here we present the updated results with a median 18.0 months of follow-up. Methods: Pts with uHCC, BCLC stage B or C, Child-Pugh class A, and ECOG PS ≤ 1 received 200 mg CS1003 intravenously once every 3 weeks and LEN orally (body weight ≥ 60 kg: 12 mg; < 60 kg: 8 mg) daily as 1L treatment. The primary endpoint was objective response rate (ORR) assessed by investigators per RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. Data cutoff for this final analysis was August 13, 2021. Results: At data cutoff, a total of 20 pts had received treatment. Compared with the last preliminary analysis, confirmed ORR was changed from 30.0% to 45.0% (95% CI: 23.06%, 68.47%) with 9 pts achieving partial response. DCR was 90.0% with 9 pts having stable disease as best overall response. DOR ranged from 4.2 to 18.7+ months, and median DOR in all responders had not been reached. Median PFS was extended compared with the previous study readout from 8.4 months to 10.4 months (95% CI: 6.2, not estimable) with 6-month and 12-month PFS rates of 85.0% and 48.2%, respectively. Median OS had not been reached. All adverse events (AEs) were grade 1-3. Grade 3 AEs attributed to CS1003 and/or LEN occurred in 9 (45.0%) pts with the most common being gamma-glutamyltransferase increased (2 pts, 10.0%). Six (6) pts experienced grade 3 CS1003-related AEs, among whom, 4 pts also experienced grade 3 AEs related to LEN. Only 2 pts discontinued treatment due to AEs. There were no deaths due to AEs, and no new safety signals were identified. Conclusions: The antitumor activity of CS1003 + LEN combination as 1L treatment in Chinese pts with uHCC remains encouraging and durable through a longer follow-up period, and the safety profile is well tolerated and manageable. The PFS is longer and the ORR is higher compared to the data previously reported, which support further development as a combination treatment for improving outcomes in uHCC pts. The ongoing multi-regional, double-blinded, randomized, placebo-controlled, phase 3 trial (CS1003-305, NCT04194775) is currently recruiting and will further evaluate adding CS1003 to LEN as a 1L treatment in uHCC. Clinical trial information: NCT03809767.

LBA4008 Background: First-line therapies based on programmed death ligand 1 (PD-L1) inhibitors are standard of care (SOC) in uHCC and demonstrate improved outcomes over SOR; however, prognosis remains poor and there is an unmet need for alternative therapies with long-term benefits. Second-line NIVO + IPI demonstrated clinically meaningful efficacy and manageable safety in SOR-treated patients (pts) with HCC in CheckMate 040, leading to its accelerated approval in the United States. We report first results from the preplanned interim analysis of the phase 3, open-label, randomized CheckMate 9DW trial evaluating the efficacy and safety of NIVO + IPI vs LEN or SOR as first-line therapy for pts with uHCC (NCT04039607). Methods: Adult pts with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score 5–6, and ECOG performance status 0–1 were included. Pts were randomly assigned 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles) followed by NIVO 480 mg Q4W or investigator’s choice of LEN 8 mg or 12 mg QD or SOR 400 mg BID until disease progression or unacceptable toxicity. NIVO was given for a maximum of 2 years. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR) and duration of response (DOR) per blinded independent central review (BICR) using RECIST v1.1. Results: In total, 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333); among 325 pts treated in the LEN/SOR arm, 275 (85%) received LEN. After a median (range) follow-up of 35.2 (26.8–48.9) months (mo), median OS was 23.7 mo with NIVO + IPI vs 20.6 mo with LEN/SOR (HR, 0.79; 95% CI, 0.65–0.96; P = 0.0180) (Table), with respective 24-mo OS rates (95% CI) of 49% (44–55) vs 39% (34–45). ORR was higher with NIVO + IPI (36%) vs LEN/SOR (13%; P < 0.0001); complete response was observed in 7% of pts with NIVO + IPI vs 2% with LEN/SOR. Median DOR was 30.4 mo with NIVO + IPI vs 12.9 mo with LEN/SOR (Table). A summary of treatment-related adverse events (TRAEs) is shown in the Table. Conclusions: NIVO + IPI demonstrated statistically significant OS benefit vs LEN/SOR in pts with previously untreated uHCC, as well as higher ORR and durable responses with a manageable safety profile. These results support this combination as a potential new first-line SOC for uHCC. Clinical trial information: NCT04039607 . [Table: see text]

Evolution of systemic therapy for advanced HCC patients: Did we make progress in 2022?

520 Background: In the phase 3 CheckMate 9DW study (NCT04039607), 1L NIVO + IPI demonstrated significant overall survival (OS) benefit vs LEN/SOR, higher objective response rate (ORR) with durable responses, and manageable safety in uHCC. We present efficacy by best overall response (BOR) subgroups and baseline characteristics, and additional safety analyses from the preplanned interim analysis. Methods: Patients (pts) with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score 5 or 6, and ECOG performance status 0 or 1 were randomized 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles), then NIVO 480 mg Q4W or LEN 8 mg or 12 mg QD or SOR 400 mg BID until disease progression or unacceptable toxicity. NIVO was given for a maximum of 2 years. The primary endpoint was OS; secondary endpoints included ORR and duration of response (DOR) per blinded independent central review (BICR) using RECIST v1.1. Results: A total of 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333). At a median follow-up of 35.2 (range 26.8–48.9) months (mo), median OS (95% CI) was 23.7 (18.8–29.4) mo with NIVO + IPI vs 20.6 (17.5–22.5) mo with LEN/SOR (HR 0.79 [95% CI 0.65–0.96]; P = 0.0180). ORR (95% CI) per BICR was significantly higher with NIVO + IPI vs LEN/SOR (36% [31–42] vs 13% [10–17]; P < 0.0001); median DOR (95% CI) was 30.4 (21.2–not estimable [NE]) mo vs 12.9 (10.2–31.2) mo. Survival benefit of NIVO + IPI vs LEN/SOR was observed across BOR subgroups at the 24-week landmark timepoint (Table). In subgroup analyses, ORR (95% CI) per BICR was higher with NIVO + IPI vs LEN/SOR across HCC etiologies (uninfected: 35% [26–44] vs 8% [4–15]; HBV infected: 25% [17–34] vs 17% [10–25]; HCV infected: 50% [39–61] vs 16% [9–25]) and in pts with Barcelona Clinic Liver Cancer stage ≤B (33% [23–43] vs 13% [6–21]) or stage C (37% [31–44] vs 14% [10–19]). Safety data are shown in the Table. Additional exploratory analyses will be presented. Conclusions: These additional analyses from CheckMate 9DW demonstrate the efficacy and manageable safety of 1L NIVO + IPI in uHCC and further support its use as a potential standard-of-care treatment option in this setting. Clinical trial information: NCT04039607 . OS by BOR at week 24 landmark NIVO + IPI LEN/SOR BOR CR + PR (n = 101) SD a (n = 105) PD (n = 47) CR + PR (n = 28) SD a (n = 212) PD (n = 31) Median OS (95% CI), mo NR (44.4–NE) 30.0(23.5–37.8) 16.0(12.0–18.7) 28.3(20.6–NE) 22.5(20.5–24.8) 13.5(8.7–25.3) All treated pts NIVO + IPI (n = 332) LEN/SOR (n = 325) Any-grade/grade 3–4 TRAEs, n (%) 278 (84)/137 (41) 297 (91)/138 (42) Hepatobiliary 44 (13)/35 (11) 15 (5)/10 (3) Cardiovascular 10 (3)/3 (< 1) 138 (42)/39 (12) Hemorrhagic 2 (< 1)/1 (< 1) 20 (6)/5 (2) a Includes non-CR/non-PD. CR, complete response; NR, not reached; PD, progressive disease; PR, partial response; SD, stable disease; TRAE, treatment-related adverse event.

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Management of patients with hepatitis B virus-induced cirrhosis

In the twentieth session of the National Clinical Oncology Conference and 2017 annual meeting of Chinese Society of Clinical Oncology (CSCO), many progre-ssions have been made in the diagnosis and treatment of primary liver cancer. (1) A preliminary report of the real world study of primary liver cancer in China was released. (2) Emerging diagnostic techniques and predictive models can detect preoperative liver cirrhosis and risk of postoperative liver failure in patients with hepatocellular carcinoma (HCC). (3) Photodynamic diagnostic technology can ensure histological clearance with nega-tive surgical margin and preserve as much liver parenchyma as possible. (4) Lenvatinib is expected to be the first-line targeted drug for the treatment of patients with unresectable HCC following sorafenib. (5) Immunotherapy with Nivolumab and Pembro-lizumab is still a hot topic in the field of HCC management. (6) Though a vast heterogeneity of patterns of liver resection for HCC exists between two large centers from the East and the West, their surgical safety and long-term efficacy are actually comparable. (7) Routine lymphadenectomy, active surgical intervention for patients with late-stage tumors, ensuring the negative margins of resection and comprehensive treatment of postoperative recurrence are expected to improve the long-term outcomes of intrahepatic cholangiocarcinoma (ICC). Key words: Liver neoplasms, primary; Sorafenib; Lenvatinib; Targeted therapy; Immunotherapy

3503 Background: NIVO + IPI demonstrated superior progression-free survival (PFS) vs chemo in patients (pts) with previously untreated MSI-H/dMMR mCRC in the randomized phase 3 CheckMate 8HW study (NCT04008030). We report expanded efficacy analysis from the prespecified interim analysis of NIVO + IPI vs chemo in the 1L setting. Methods: Pts with unresectable or mCRC and MSI-H/dMMR status by local testing were enrolled across different lines of therapy and randomized 2:2:1 to NIVO (240 mg) + IPI (1 mg/kg) Q3W (4 doses, then NIVO 480 mg Q4W), NIVO (240 mg) Q2W (6 doses, then NIVO 480 mg Q4W), or chemo ± targeted therapies; treatments continued until disease progression or unacceptable toxicity (all arms) or for up to 2 years (NIVO ± IPI arms). In pts with blinded independent central review (BICR)–documented progression with chemo, crossover to NIVO + IPI was permitted. Dual primary endpoints were PFS by BICR per RECIST v1.1 for NIVO + IPI vs chemo (1L) and NIVO + IPI vs NIVO (all lines) in pts with centrally confirmed MSI-H/dMMR mCRC. PFS2 (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death) was a key exploratory endpoint. Results: Among 303 pts randomized to NIVO + IPI (n = 202) or chemo (n = 101), 171 pts in the NIVO + IPI arm and 84 pts in the chemo arm had centrally confirmed MSI-H/dMMR. At 31.5-months (mo) median follow-up (range 6.1–48.4), NIVO + IPI demonstrated superior PFS vs chemo (HR 0.21; 97.91% CI 0.13–0.35; P &lt; 0.0001). Subsequent systemic therapy was received by 20 (12%) and 57 (68%) pts in the NIVO + IPI and chemo arms, respectively. In the chemo arm, 56 (67%) pts received subsequent immunotherapy (39 [46%] crossed over to NIVO + IPI on study; 17 [20%] received non-study immunotherapy). Median PFS2 was not reached (NR) with NIVO + IPI and 29.9 mo with chemo (HR 0.27; 95% CI 0.17–0.44; Table). Any grade and grade 3/4 treatment-related adverse events (TRAEs) are presented (Table). Treatment-related deaths were reported for 2 pts in the NIVO + IPI arm. Conclusions: Clinical benefit with 1L NIVO + IPI vs chemo was maintained after subsequent therapy, as shown by improved PFS2 in pts with centrally confirmed MSI-H/dMMR mCRC. No new safety concerns were identified with NIVO + IPI. These results further support NIVO + IPI as a standard-of-care 1L treatment option for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT04008030 . [Table: see text]

Background: Several tyrosine kinase inhibitors (TKIs) have been developed for hepatocellular carcinoma (HCC). However, their efficacy is limited partly due to the diversity of its genetic drivers. In this study, we sought for HCC oncogenes involved in susceptibility of TKIs and aimed to develop their serum biomarkers. Methods: We created a novel HCC mouse model in which tumor diversity of genetic drivers was recapitulated by transposon-based intrahepatic delivery of a pooled barcode-tagged 10-oncogene cDNA library. Tumor-bearing mice were then treated with lenvatinib (LEN), or sorafenib (SOR), or vehicle until moribund. The relative abundance of each oncogene cDNA in each tumor was quantified by a high-throughput barcode sequence. In vitro LEN susceptibility was assessed in 9 human HCC cell lines and LEN-resistant Hep3B cells (LEN-R) established by its long-term exposure. Tumor-derived secreted proteins were screened via cellular proteomic and secretomic analyses of Huh7 and Hep3B cells. Serum and tumor levels of identified proteins were examined in 62 HCC patients who underwent hepatectomy. Efficacy of biomarker candidates was assessed using pre-treated serum of 96 HCC patients who underwent TKI therapy. Results: Mice developed multiple genetically heterogeneous liver tumors as early as 2 weeks after delivery of the pooled library. Upon TKI administration, their sequencing analysis showed that LEN selectively eliminated FGF19-expressing tumors, whereas SOR did MET- and NRAS-expressing tumors. Among 9 HCC cell lines, HuH7 and Hep3B cells showed the highest FGF19 levels and LEN susceptibility. FGF19 inhibition eliminated their susceptibility. LEN-R cells showed reduction of FGF19 levels and got resensitized to LEN by FGF19 replenishment. Thus, FGF19-driven HCC is susceptible to LEN. Proteomics identified 6 secreted proteins downregulated by FGF19 inhibition in Hep3B cells. Among them, ST6GAL1 was the most positively correlated with FGF19 in HCC cell lines and in mouse and human HCC tissues. FGF19 knockdown in Hep3B cells decreased phosphorylation of STAT3, whereas FGF19 overexpression increased its phosphorylation with ST6GAL1 upreguation. Silencing of STAT3 signal by inhibitor or siRNA significantly decreased ST6GAL1 expression. In surgically-resected HCC patients, serum ST6GAL1 levels were positively correlated with tumor site FGF19 expression and were markers for disease progression. In TKI-treated HCC patients with high baseline serum ST6GAL1 levels, LEN therapy showed significantly longer survival than SOR. Conclusion: ST6GAL1 is a tumor-derived secreted protein downstream of FGF19 and may be a useful serum biomarker for identification of patients with FGF19-driven HCC who may benefit from LEN therapy. Citation Format: Yuta Myojin, Takahiro Kodama, Hayato Hikita, Ryotaro Sakamori, Tetsuo Takehara. Serum ST6GAL1 is a novel biomarker for predicting efficacy of tyrosine kinase inhibitors in hepatocellular carcinoma by detecting FGF19 expressing tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 351.

Hyperprogression in hepatocellular carcinoma: Illusion or reality?

4078 Background: The randomized phase 3 REFLECT trial demonstrated that LEN was non-inferior to SOR in overall survival (OS; primary endpoint) in 1L uHCC (median: 13.6 months [95% CI, 12.1–14.9] vs 12.3 months [95% CI, 10.4–13.9]) (HR, 0.92; 95% CI, 0.79–1.06). Median progression-free survival (PFS) by independent imaging review (IIR) per mRECIST was 7.3 months (95% CI, 5.6–7.5) for pts in the LEN arm and 3.6 months (95% CI, 3.6–3.7) for pts in the SOR arm (HR, 0.64; 95% CI, 0.55–0.75; p&lt;0.0001). Objective response rate (ORR) by IIR per mRECIST was 40.6% for pts in the LEN arm and 12.4% for pts in the SOR arm (odds ratio, 5.01; 95% CI, 3.59–7.01; p&lt;0.0001) [Kudo 2018, Lancet]. Since REFLECT, combination therapies with immunotherapy have become part of the therapeutic arsenal for the treatment of uHCC, and many studies are ongoing. Recent data suggest that viral/nonviral etiology may impact treatment outcomes [Pfister 2021, Nature; Rimini 2022, ESMO Open]. To add to the current body of evidence, this post hoc analysis evaluated efficacy in pts with nonviral etiology in REFLECT. Methods: In REFLECT, pts with uHCC who had not received treatment for advanced disease were randomized to LEN (12 mg/day for bodyweight ≥60 kg; 8 mg/day for bodyweight &lt;60 kg) or SOR (400 mg twice-daily) in 28-day cycles. This post hoc analysis included pts without hepatitis B or C (based on medical history) who were randomized to receive LEN or SOR. PFS, ORR (by IIR per mRECIST), and OS were analyzed. OS and PFS were estimated with the Kaplan-Meier method. Results: Of 478 pts randomized to LEN and 476 pts randomized to SOR, 127 and 108 pts, respectively, had nonviral etiology. Among randomized pts with nonviral etiology, median OS was 13.8 mos (95% CI, 10.5–18.7) in the LEN arm and 13.9 months (95% CI, 11.7–17.5) in the SOR arm (HR, 1.03; 95% CI, 0.75–1.43). Median PFS was 7.4 months (95% CI, 5.5–8.7) in pts randomized to LEN with nonviral etiology and 4.0 months (95% CI, 3.6–5.5) in pts randomized to SOR with nonviral etiology (HR, 0.60; 95% CI, 0.42–0.87). ORR was 39.4% (95% CI 30.9–47.9) in pts randomized to LEN with nonviral etiology and 20.4% (95% CI 12.8–28.0) in pts randomized to SOR with nonviral etiology. Fewer (n=34 [26.8%]) pts with nonviral etiology randomized to LEN received anticancer medication during survival follow-up than those randomized to SOR (n=46 [42.6%]). Conclusions: In this post hoc analysis, OS, PFS, and ORR in pts randomized to LEN with nonviral etiology were consistent with the overall population of pts randomized to LEN. This post hoc analysis, along with the results of the primary analysis of REFLECT [Kudo 2018, Lancet], demonstrates the efficacy of LEN regardless of etiology in uHCC, and supports LEN as a standard of care option for pts with 1L uHCC. Treatment efficacy by etiology should be assessed prospectively in future uHCC trials. Clinical trial information: NCT01761266 .

LBA4_PR - Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 part 1 final analysis

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 &lt; 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 &lt; 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 &lt; 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 &lt; 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

Introduction: Checkpoint inhibitors have demonstrated activity in brain lesions in several tumor types, including NSCLC. CheckMate 227 Part 1 (NCT02477826) met its two independent co-primary endpoints, including improved overall survival (OS) for NIVO + IPI vs histology-based chemotherapy (chemo) in patients (pts) with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. Benefit was also observed in pts with PD-L1 &amp;lt; 1%. Eligible pts included those with treated, asymptomatic brain metastases (mets). Here we present a post-hoc analysis of efficacy and safety in pts with and without baseline (BL) brain mets. Methods: Eligible pts were chemo-naive, with stage IV or recurrent NSCLC, no known sensitizing EGFR/ALK alterations, and ECOG PS 0–1. Pts with treated brain mets who were asymptomatic for ≥ 2 wks prior to randomization were eligible; corticosteroids equivalent to ≤ 10 mg of prednisone daily were permitted if stable or decreasing for ≥ 2 wks prior to randomization. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 240 mg Q2W, or chemo; pts with PD-L1 &amp;lt; 1% (n = 550) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 360 mg Q3W + chemo, or chemo. Pts were treated until disease progression, unacceptable toxicity, or ≤ 2 y of immunotherapy. Results: BL characteristics were generally similar between pts with and without BL brain mets, except that a greater proportion of pts with BL brain mets were &amp;lt; 65 years of age and had non-squamous histology. Efficacy data are shown in the Table. Any-grade nervous system adverse events were reported in 46% of pts with BL brain mets treated with NIVO + IPI and 42% of those treated with chemo, most were grade 1–2. Conclusion: In this post-hoc analysis of pts with advanced NSCLC, NIVO + IPI appeared to provide similar benefit in pts with and without BL brain mets. No new safety signals were identified. Table.Efficacy by baseline brain metastases in CheckMate 227 Part 1Patients with baseline brain metastasesPatients without baseline brain metastasesNIVO + IPI (n = 69)Chemo (n = 66)NIVO + IPI (n = 514)Chemo (n = 517)OS, median (95% CI), mo18.8 (9.2-29.4)13.7 (10.5-16.2)17.1 (15.3-19.9)13.9 (11.8-15.3)HR (95% CI)0.57 (0.38-0.85)0.76 (0.66-0.88)1-y rates, %575962542-y rates, %44264030PFS,a median (95% CI), mo5.4 (3.1-8.6)5.8 (4.3-8.0)4.9 (4.1-5.7)5.4 (4.5-5.6)HR (95% CI)0.79 (0.52-1.19)0.81 (0.70-0.93)1-y rates, %382132172-y rates, %227206ORR,a %33263328DOR,a median (95% CI), mo24.9 (11.3-NR)8.4 (4.2-13.9)19.6 (15.5-28.6)5.8 (4.8-6.9)1-y rates, %724065262-y rates, %5384610Minimum follow-up was 29.3 mo.aPer BICR. BICR, blinded independent central review; CI, confidence interval; chemo, chemotherapy; DOR, duration of response; HR, hazard ratio; IPI, ipilimumab; mo, month; NIVO, nivolumab; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; y, year. Citation Format: Hossein Borghaei, Adam Pluzanski, Reyes Bernabe Caro, Mariano Provencio, Sjaak Burgers, Enric Carcereny, Keunchil Park, Aurelia Alexandru, Lorena Lupinacci, Randeep Sangha, Judith Raimbourg, Alain Vergnenegre, Konstantinos Syrigos, Fabrice Barlesi, Norbert Frickhofen, Ang Li, Ravi Kasinathan, Luis Paz-Ares. Nivolumab (NIVO) + ipilimumab (IPI) as first-line (1L) treatment for patients with advanced non-small cell lung cancer (NSCLC) with brain metastases: Results from CheckMate 227 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT221.

122MO Nivolumab (NIVO) + ipilimumab (IPI) as first-line (1L) treatment (tx) for patients (pts) with advanced NSCLC (aNSCLC) and baseline (BL) brain metastases (mets): Intracranial and systemic outcomes from CheckMate 227 Part 1