Study Of Nivolumab In Combination Research Articles

A Phase 2 study of nivolumab in combination with modified FOLFIRINOX for metastatic pancreatic cancer

BackgroundNivolumab with modified FOLFIRINOX (mFOLFIRINOX) may have additive antitumour effects while minimising chemotherapy cytotoxicity. We assessed the efficacy and safety of nivolumab+mFOLFIRINOX in metastatic pancreatic cancer.MethodsThirty-one treatment-naïve patients aged ≥20 years with metastatic unresectable/recurrent pancreatic cancer (≥1 measurable lesion per Response Evaluation Criteria in Solid Tumours version 1.1) and Eastern Cooperative Oncology Group 0/1 score and life expectancy ≥90 days received nivolumab (480 mg, every 4 weeks) plus mFOLFIRINOX. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS) and safety.ResultsAt the median follow-up of 13.4 months, the ORR was 32.3% (complete response 0%; partial response 32.3%) and the median duration of response was 7.4 (range: 3.5–21.9) months; the primary endpoint was not met. Median OS and PFS were 13.4 (95% confidence interval [CI]: 10.6–16.6) months and 7.4 (95% CI: 3.9–9.2) months, respectively. The 1-year survival rate was 54.8% (95% CI: 36.0%–70.3%). Drug-related serious adverse events were reported in 29.0% of the patients; 3.2% drug-related adverse events led to discontinuation, and none led to death within 30-day safety window.ConclusionNivolumab+mFOLFIRINOX was tolerable in patients with metastatic pancreatic cancer. ORR and survival were comparable to previously reported data. (JapicCTI-184230)

METRO-PD1: Phase 1 study of nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumors

BackgroundThis multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors. Objectives: To evaluate the feasibility and safety of the three regimens MethodsPatients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C). Arm A and B were allocated sequentially. Arm C opened only if A and B were deemed safe. Dose-limiting toxicities (DLTs) were evaluated over the first two cycles. Patients were evaluable if they received > 2 cycles and > 70% of the planned dose. PopulationSixteen patients were enrolled, 3 in arm A, 6 in arm B, and 7 in arm C. Median age was 11.5 years (range, 5–19). Patients previously received a median of 3.5 (range, 1–4) lines of systemic treatment, 14 patients had surgery and 11 had radiotherapy. ResultsMedian number of cycles was 2 (1−24), median treatment duration was 56 days (18−714). In arm C, median number of cycles was 4 with median treatment duration of 95 days. No DLT was observed. Grade 3 adverse events (AE) and serious AE were observed in 8 patients (50%) and 1 patient (6%), respectively, over the first 2 cycles. No grade 4 AE occurred. The 6-month PFS and OS were 12% and 44%, respectively, in the whole population. Prolonged stable disease was observed in a high-grade glioma and an atypical teratoid rhabdoid tumor. ConclusionArm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing.

A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ. Three dose limiting toxicities are reported at the highest dose cohorts. We report only one patient with any immune related adverse event (irAE). No irAEs ≥ grade 3 are observed and no patients require corticosteroids. The maximum tolerated dose of IFN-γ is 75 mcg/m2, however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m2. Exploratory analyses of efficacy in the phase I cohorts demonstrate one patient with a complete response, and five have achieved stable disease. Pre-planned correlative assessments of circulating immune cells demonstrate intermediate monocytes with increased PD-L1 expression correlating with IFN-γ dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-γ induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456.

A phase II trial of neoadjuvant nivolumab, docetaxel, and cisplatin therapy followed by surgery and radiation therapy for resectable high-grade salivary gland carcinoma.

TPS6110 Background: Salivary gland carcinomas (SGCs) are rare entities that contribute to approximately 5% of head and neck malignancies. The current standard therapy for resectable SGC is complete surgical resection with adjuvant radiotherapy or chemoradiotherapy. However, the patients with high-grade histological subgroup tumors have the highest risk of regional and distant metastasis as the primary cause of treatment failure.. The previous evidence demonstrates that neoadjuvant chemotherapy showed a statistically significant advantage in survival for patients with head and neck cancer. Based on the success of neoadjuvant immune checkpoint inhibitors (ICI) in preventing disease recurrence and achieving pathologic complete response (pCR) in different types of cancer, we designed this study by incorporating nivolumab combined with neoadjuvant cytotoxic chemotherapy in patients with potentially resectable high-grade SGCs. Methods: This study is the phase II, open-label, single-center study of nivolumab in combination with docetaxel, and cisplatin as a neoadjuvant therapy in high-grade resectable SGCs. All the patients must be confirmed with pre-defined high-grade histology and clinically node-positive. As the representative inclusion/exclusion criteria, all the patients must not receive prior cancer therapy in advance to study enrollment, including another kind of immunotherapy, cytotoxic chemotherapy, or radiotherapy. Three cycles of nivolumab (360mg), docetaxel (60mg per m2), and cisplatin (60mg per m2) are applied every three weeks. Three weeks after the last treatment, the patient is re-evaluated for the surgery and will undergo surgery within seven weeks after the last treatment. Based on the surgical pathologic outcome, additional radiotherapy will be initiated between 4 to 8 weeks after the surgery per the following guidance; R0: 59.4Gy/25fx; R1 or R2: 59.4Gy/25fx with optional boost 6.6Gy/3fx. The primary objective is the major pathologic response rate defined by ≤ 10% of tumors composed of viable tumors. Complete resection rate, response rate, downstaging at pathologic staging, two-year distant metastasis free-survival, disease-free survival, overall survival, safety results, surgical outcomes of facial nerve function, completeness of post-neoadjuvant surgery will be analyzed as the secondary objectives. The sample size was calculated using H0 of mPR ≤25% and H1 of mPR ≥50%, according to the one-arm binomial model (power of 90% and one-sided alpha of 0.05). A total of 50 patients will be recruited, include 40 evaluable patients. This study is currently recruiting patients at Samsung Medical Center, South Korea. The first subject received treatment in Nov. 2022 and three patients received the treatment. The time point for the primary analyses is Q3.2025. (ONO-4538-X78). Clinical trial information: NCT05727410 .

Novel Therapies for De Novo or Relapsed/Refractory AML with TP53 Mutations : A Glimmer of Hope

Background: The prognosis of TP53 mutated acute myeloid leukemia (AML) is dismal. Due to their correlation with universally bad outcomes, TP53 mutations play a crucial role in risk assessment and treatment selection in 5-10% of AML cases. Traditional Therapies have shown limited response and poor overall survival (OS). With current therapy, the median OS of a patient with newly diagnosed TP53m-AML is 6-9 months, and only around 10% of patients survive three years after allogenic hematopoietic stem cell transplantation (alloHCT). We present the safety and efficacy of novel therapeutic agents that target specifically TP53 mutated AML. Materials & Method: A comprehensive literature search was performed on PubMed, Cochrane Library, Embase, and Web of Science. We used the following mesh terms and Emtree terms, "acute myeloid leukemia" OR "AML" AND "TP53 mutations" from the inception of literature till 06/01/2022. We screened 2300 articles and included articles citing novel therapies such as "Venetoclax" (VEN), "Hypomethylating agents (HMA), 5-azacytidine (5-AZA), "checkpoint inhibitors, and "MDM2 inhibitors". We extracted data for "complete response (CR), Overall Survival (OS), and Progression-free survival (PFS) and safety variables such as grade III-IV adverse events. We excluded case reports, case series, preclinical trials, single-arm studies, review articles, meta-analyses, and controlled. STATA version 14.2 was used. Results: A total of 1814 patients were included in three-phase III and eleven phase II trials. Bcl-2 inhibitors :For VEN in combination with two phase III trials incorporating 641 patients were evaluated; In both trials, encouraging remission rates were reported in de-nov or relapsed or refractory patients harboring TP53 mutations. However, the median OS was 14.7 vs 5.17 (mTP53 vs wTP53) months in the treatment group compared to 4.9 vs 9.6 (mTP53 vs wTp53) months in the control group respectively. For VEN +AZA combination group, CR rates in mTP53 patients was 55% versus 0% in AZA alone (p < 0.001). VEN with low-dose cytarabine (LDAC) had 27% CR, whereas LDAC alone had 7%. Checkpoint inhibitors such as nivolumab showed favorable responses, as in the phase II study of nivolumab in combination with azacitidine in relapsed/refractory (R/R) AML; it demonstrated acceptable toxicity and an overall response rate (ORR) of 33%. However, increased response rates were seen in HMA-naïve patients. HDAC inhibitors : In two phase II trials incorporating AZA vs AZA + entinostat, the CR was 46% vs 44% . The mOS achieved in AZA was 18 months vs. combination therapy with entinostat. In the study by Manero et al. , the combination therapy of Decitabine and valproic acid showed CR of 34% and mOS of 11.9 months. The results of other trials with respect to TP53 mutation is shown in table 1. APR-246 inhibitors: In two phase II trials combining Eprentapopt with AZA , 29 patients were enrolled and CR of 41% was achieved.Sallman et al. described a remission of 82% with a median OS of 14.7 months in Eprenetapopt + 5-AZA. The most common grade ≥ 3 hematological adverse events were anemia, neutropenia, thrombocytopenia, and leukopenia. MDM2 Inhibitors : In the MIRROS trial, a phase III trial incorporating idasanutlin + cytarabine + placebo + cytarabine in R/R AML;436 patients were enrolled. The CR was 20.3%vs 17.1%(odds ratio [OR], 1.23; 95%CI, 0.70-2.18). Common any-grade adverse events (≥ 10%incidence in any arm) were diarrhea (87.0%vs 32.9%), febrile neutropenia (52.8%vs 49.3%), and nausea (52.5%vs 31.5%). The grade ≥3 hematological and non-hematological adverse events have been reported in Table 1. Conclusion: Emerging therapies employ unique therapeutic pathways that have led to increased optimism regarding the therapeutic potential of TP53 mutations. Although the median OS remains approximately a year with these therapies, hypomethylating drugs in combination with VEN or as independent therapy demonstrated greater response rates than induction chemotherapy. Initial progress has resulted from eprenetapopt's direct targeting of mutant p53 protein, showing a favorable 82% complete response. Still a daunting challenge, a combination of these therapies may ultimately be necessary to obtain adequate and sustained responses. Participation in clinical trials for all newly diagnosed AML patients should be encouraged to promote the development of innovative therapeutics. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract CT022: CheckMate 848: A randomized, open-label, phase 2 study of nivolumab in combination with ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden

Abstract High tumor mutational burden assessed in tissue biopsies (tTMB-H) or blood (bTMB-H) is associated with clinical efficacy in patients treated with immunotherapies. CheckMate 848 (NCT03668119) is a prospective phase 2 study of nivolumab (NIVO) with or without ipilimumab (IPI) in patients with advanced or metastatic solid tumors that are tTMB-H or bTMB-H (≥ 10 mutations/megabase) who were immunotherapy-naive and refractory to standard local therapies. The primary endpoint was objective response rate (ORR) in patients with tTMB-H or bTMB-H, assessed by FoundationOne® CDx-based and Clinical Trial Assays (Foundation Medicine), respectively. The study was not powered to compare NIVO + IPI vs NIVO. We present the interim and final analyses for the tTMB-H and bTMB-H cohorts, respectively (≥ 12 months follow-up, database lock June 2021). Of 1954 screened patients, 212 were randomized 2:1 to NIVO 240 mg Q2W + IPI 1 mg/kg Q6W or NIVO 480 mg Q4W for ≤ 24 months, and 201 (135 tTMB-H; 147 bTMB-H) were refractory to standard therapies. Of &amp;gt; 40 tumor types, colorectal (10.8%), small-cell lung (7.5%), breast (7.1%), and uterine (7.1%) were the most common. ORR and survival outcomes with NIVO + IPI were improved in patients with tTMB-H. The responses were independent of bTMB-H status in the tTMB-H cohort but improved with tTMB-H status in the bTMB-H cohort (Table). The safety profile of NIVO + IPI was manageable, and clinical outcomes with NIVO were comparable with previous studies. The impact of TMB cutoff, PD-L1 expression, and microsatellite instability were explored. In conclusion, NIVO + IPI demonstrated clinical efficacy with a manageable safety profile in patients with advanced or metastatic solid tumors that are tTMB-H or bTMB-H and refractory to standard therapies, with increased efficacy observed in patients with tTMB-H. NIVO + IPI tTMB-H cohort bTMB-H cohorta Patients, n (%)b,c 68 (32.1) 80 (37.7) Number of prior treatments, median (range) 2 (0–7) 2 (1–9) ORR, n (%)c, 95% CI 24 (35.3), 24.1–47.8 18 (22.5), 13.9–33.2 ORR in patients with bTMB-H by tTMBc: &amp;lt; 10 mut/Mb (n = 31), n (%), 95% CI NA 3 (9.7), 2.0–25.8 ≥ 10 mut/Mb (n = 39), n (%), 95% CI NA 13 (33.3), 19.1–50.2 ≥ 10 to &amp;lt; 16 mut/Mb (n = 18), n (%), 95% CI NA 3 (16.7), 3.6–41.4 ≥ 16 mut/Mb (n = 21), n (%), 95% CI NA 10 (47.6), 25.7–70.2 ORR in patients with tTMB-H by bTMBc: &amp;lt; 10 mut/Mb (n = 20), n (%), 95% CI 7 (35.0), 15.4–59.2 NA ≥ 10 mut/Mb (n = 43), n (%), 95% CI 16 (37.2), 23.0–53.3 NA ≥ 10 to &amp;lt; 16 mut/Mb (n = 12), n (%), 95% CI 3 (25.0), 5.5–57.2 NA ≥ 16 mut/Mb (n = 31), n (%), 95% CI 13 (41.9), 24.5–60.9 NA Percentage of responders (≥ 9 months) (95% CI) 91 (68–98) 88 (61–97) Median PFS, months (95% CI)c 4.1 (2.8–11.3) 2.8 (2.3–3.0) Median OS, months (95% CI)c 14.5 (7.7–NE) 8.5 (5.8–10.5) aThe bTMB cohort was randomized prior to December 20, 2019. bOut of 212 randomized patients; data presented in this table are from patients who were refractory to standard therapies. cMinimum follow-up 12 months. bTMB, blood tumor mutational burden; NA, not applicable; NE, not evaluable; PFS, progression-free survival; OS, overall survival; tTMB, tissue tumor mutational burden. Citation Format: Michael Schenker, Mauricio Burotto, Martin Richardet, Tudor Ciuleanu, Anthony Goncalves, Neeltje Steeghs, Patrick Schöffski, Paolo A. Ascierto, Michele Maio, Iwona Lugowska, Lorena Lupinacci, Alexandra Leary, Jean-Pierre Delord, Julieta Grasselli, David S. Tan, Jennifer E. Friedmann, Jacqueline Vuky, Marina Tschaika, Ruta Slepetis, Georgia D. Kollia, Misena Pacius, Ning Huang, Parul Doshi, Jonathan Baden, Massimo Di Nicola. CheckMate 848: A randomized, open-label, phase 2 study of nivolumab in combination with ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT022.

Phase II study of nivolumab in combination with FOLFOXIRI/bevacizumab as first-line treatment in patients with advanced colorectal cancer RAS/BRAF mutated (mut): NIVACOR trial (GOIRC-03-2018).

3509 Background: FOLFOXIRI plus bevacizumab (BEV) represents standard chemotherapy in first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC). The NIVACOR study evaluates the addition of nivolumab (NIV) to FOLFOXIRI/BEV as first-line therapy in mCRC RAS/BRAF mut pts regardless of MSS/MSI status. Methods: This is a single-arm, multicenter, open-label, phase II trial in first-line treatment of pts with mCRC RAS/BRAF mut. Pts received NIV at a flat dose of 240 mg q14 days, FOLFOXIRI (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and 5-fluorouracil CI 3,200 mg/m2 for 48 hours) in combination with BEV at the dose of 5 mg/kg IV q14 days for eight cycles and then, the maintenance with BEV/NIV until PD or unacceptable toxicities. The primary endpoint was the ORR according to RECIST 1.1 Criteria. All images are reviewed by Independent Data Monitoring Committee. According to Fleming’s design with alpha and beta levels of 0.05 and 0.2 respectively, in a sample size of 73 pts (comprehensive of a 10% drop-out rate), at least 56 responses were necessary to not reject the alternative hypothesis of an ORR=0.80. Results: From October 2019 to March 2021, 73 pts were enrolled in 9 Italian centers. The median age was 60 (51-65) years and 50.7% were male; the main primary tumor side was right (50.7%). The molecular characterization was: 87.7% RAS mut, 16.2% BRAF mut, and 4.5% both RAS and BRAF mut; 10/62 were MSI (16.1%), 52/62 (83.9%) MSS, and 11 pts not assessed. Liver metastases were present in 56.2% pts. The median follow-up was 14.3 (IQR 11.5-16.5) months on December 31, 2021. The median (m) duration of treatment was 12 (8-17) cycles. The ORR was 76.7%, with 7(9.6%) CR and 49(67.1%) PR. SD were 15(20.6%) with a DCR of 97.3%; 2(2.7%) pts were not evaluable. The mDOR was 8.4 (95%CI, 7-NE) months. The mPFS was 10.1 months (95%CI, 9.4-NE) and 12-months PFS was 53.4%. At data cut-off, 65 (89.1%) pts are still alive. In subgroups analysis of MSS pts the ORR was 78.9% with a mDOR of 7.59 (95% CI 6.21 -11.43) months, DCR of 96.2%, and mPFS of 9.8 (95%CI 8.18-15.24) months. The surgery of the primary tumor, metastases, or both was performed in 6(8.2%), 9(9.6%), and 5(6.9%) of pts, respectively. The main grade (G) 3 -4 toxicities were: neutropenia (G3 21.9%, G4 15.1%), diarrhea (G3 17.8%, G4 1.4%), hypertension G3 (6.8%), fatigue G3 (6.8%), and febrile neutropenia G4 (4.1%). Conclusions: The primary endpoint ORR was met. These results show the preliminary efficacy and safety of NIV in combination with FOLOXIRI/BEV as first-line therapy in pts with mCRC RAS/BRAF mut. Also, promising activity was observed in MSS subgroup pts. These data support the conduction of phase III randomized-controlled study. Research Sponsor: Bayer, Bristol Myers-Squibb. Clinical trial information: NCT04072198.

A phase II study of nivolumab in combination with modified FOLFIRINOX for metastatic pancreatic cancer.

553 Background: Although FOLFIRINOX and nab-paclitaxel plus gemcitabine have improved the survival of unresectable pancreatic cancer patients, high unmet medical needs still exist for the treatment of this cancer. Nivolumab has shown efficacy for multiple cancer types in not only its monotherapy but also combinations with conventional chemotherapies. This study aimed to assess the efficacy and safety of nivolumab in combination with modified FOLFIRINOX, which is one of the first line chemotherapy for pancreatic cancer. Methods: Thirty-one treatment-naïve patients with metastatic, unresectable/recurrent pancreatic cancer patients received nivolumab (480 mg, every 4 weeks) plus modified FOLFIRINOX (oxaliplatin 85 mg/m2, levofolinate 200 mg/m2, irinotecan 150 mg/m2 and fluorouracil 2400 mg/m2, every 2 weeks). The primary endpoint was objective response rate (ORR) (central assessment). Secondary endpoints were overall survival (OS), progression-free survival (PFS) (central assessment), safety etc. Results: The median duration of follow-up was 13.40 months. ORR was 32.3% (CR: 0.0%, PR: 32.3%) and the median duration of response was 7.36 (range 3.5-20.1+) months. Median OS and PFS were 13.40 (90% CI 10.87-15.24) months and 7.39 (90% CI 3.88-7.59) months, respectively. The 1-year survival rate was 54.8 (90% CI 39.1-68.1) %. The most frequently reported grade 3-4 drug-related adverse events were neutrophil count decreased (38.7%), decreased appetite (16.1%), hypokalemia (12.9%), febrile neutropenia (9.7%), nausea (9.7%) and white blood cell count decreased (9.7%). Adrenal insufficiency (3.2%) was observed as immune mediated adverse event. Conclusions: Nivolumab in combination with modified FOLFIRINOX had a manageable safety profile in patients with metastatic pancreatic cancer. Additional work is needed to determine the population who can benefit from the combination. Clinical trial information: JapicCTI-184230.

Abstract PS12-10: Phase II study of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR+, HER2- metastatic breast cancer: WJOG11418B NEWFLAME trial

Abstract Background: Currently, the standard immunotherapy treatment for anti-programmed death-ligand 1 (PD-L1)-positive triple-negative breast cancer is a combination of PD-L1 antibody and nab-paclitaxel. PD-1/PD-L1 antibody was investigated as a treatment for hormone receptor positive (HR+) breast cancer; however, the efficacy of single agents is poor. In pre-clinical studies, anti-PD-1/PD-L1 antibody, CDK4/6 inhibitors, and endocrine therapy (ET) have synergistic effects. We initiated this investigator-initiated trial to evaluate the efficacy and safety of the combination of nivolumab, abemaciclib, and ET (fulvestrant [FUL] or letrozole [LET]) as a first- or second-line treatment for patients (pts) with HR+, human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). Methods: This multicenter, multi-cohort, nonrandomized, open-label phase II study evaluated the efficacy and safety of nivolumab, abemaciclib, and ET (FUL or LET) in pts with HR+, HER2- MBC. Key eligibility criteria for the FUL cohort were: HR+, HER2- MBC with ECOG PS ≤ 1; measurable disease; no more than one ET; no prior chemotherapy for MBC; and had exhibited disease progression while receiving ET, adjuvant ET, or ≤ 12 months after adjuvant ET. Key eligibility criteria for the LET cohort were: postmenopausal HR+, HER2- MBC with ECOG PS ≤ 1; measurable disease; and no prior systemic therapy. ET as an adjuvant was permitted if the patient had a disease-free interval &amp;gt; 12 months after the completion of ET. Patients received 240 mg nivolumab on days 1 and 15, 150 mg abemaciclib twice daily, and either 500 mg FUL on days 1, 15, 29, and every 4 weeks thereafter (FUL cohort) or 2.5 mg LET once daily (LET cohort) until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Key secondary endpoints included toxicity, disease control rate (DCR: CR+PR+SD), progression-free survival (PFS), and the overall survival (OS). The threshold and expected ORR of the FUL cohort were 45% and 60%, respectively; and 32 pts would ensure a statistical power of 80% (α = 0.20). The threshold and expected ORR of the LET cohort were 55% and 75%, respectively; and 16 pts would ensure a statistical power of 80% (α = 0.20). Results: Between June and December 2019, 17 pts were enrolled (FUL cohort: n = 12, LET cohort: n = 5). One patient in the FUL cohort was excluded due to prior treatment history. Enrollment was closed and combination treatment was discontinued mid-study due to safety concerns. All pts had ≥ 1 adverse event (AE). AEs ≥ Grade 3 were observed in 91.7% and 100% of pts in the FUL and LET cohorts, respectively. Immune-related AEs ≥ Grade 3 were observed in 66.7% and 60.0% of pts in the FUL and LET cohorts, respectively. The most frequent AEs ≥ Grade 3 were elevated liver function tests (LFT; FUL cohort: 50.0%, LET cohort: 60.0%). Immune-related (elevated LFT) AEs ≥ Grade 3 were observed in 50.0% and 40.0% of pts in the FUL and LET cohorts, respectively. Severe AEs (SAEs) were observed in 50.0% and 60.0% of pts in the FUL and LET cohorts, respectively. One treatment-related patient death occurred in the LET cohort due to interstitial lung disease (ILD). ORR was 54.5% (6/11) and 20% (1/5) in the FUL and LET cohorts, respectively. DCR was 90.9% (10/11) in the FUL cohort and 80.0% (4/5) in the LET cohort. Due to the discontinuation, PFS and OS were undetermined. Conclusions: Although nivolumab + abemaciclib + FUL appeared to have activity, our findings do not support further investigation of this combination therapy due to toxicity. Toxicity profiles vary with CDK4/6 inhibitors; therefore, a different inhibitor may improve tolerability. Results of the ongoing nivolumab, palbociclib, and ET trial are awaited (CheckMate 7A8, NCT04075604). Clinical trial information: JapicCTI-194782. Citation Format: Jun Masuda, Junji Tsurutani, Norikazu Masuda, Yuko Tanabe, Tsutomu Iwasa, Masato Takahashi, Manabu Futamura, Koji Matsumoto, Kenjiro Aogi, Hiroji Iwata, Mari Hosonaga, Toru Mukohara, Kenichi Yoshimura, Toshimi Takano. Phase II study of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR+, HER2- metastatic breast cancer: WJOG11418B NEWFLAME trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-10.

Abstract A13: Clinical characteristics of responders to nivolumab plus ipilimumab (Nivo/Ipi) in metastatic uveal melanoma

Abstract In the U.S., prospective clinical trial data regarding nivolumab plus ipilimumab for metastatic uveal melanoma have yet to be reported. Here we present clinical data regarding responders to nivolumab plus ipilimumab that occurred in the context of a prospective clinical trial. NCT01585194 is an open-label, phase II study of nivolumab in combination with ipilimumab for the treatment of metastatic uveal melanoma. Patients with confirmed metastatic uveal melanoma received nivolumab 1 mg/kg followed by ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by up to 2 years of nivolumab maintenance. Response was evaluated using irRC beginning at week 12 and every 12 weeks thereafter. Responses were rare, but were seen in 3 patients, all female, with a mean age of 48. These subjects had hepatic M1b metastases (67%) and extrahepatic M1a metastasis (33%), and all three patients experienced a partial response at the first restaging, after 4 doses of Nivo/Ipi. Two additional patients, who came off study after two doses prior to response evaluation, one due to protocol-limiting hyperglycemia, and the other due to hyperuricemia and AKI, with M1b and M1a hepatic metastases, respectively, experienced partial responses. The first of these patients continued on additional Nivo/Ipi and developed a partial response 6 months after clinical trial initiation. The second patient never resumed additional treatment for metastatic disease. Her restaging scans 2 months after clinical trial initiation showed partial response; five months after initiation, her response continues with &amp;gt;70% reduction in tumor burden. Responders to Nivo/Ipi had the following immune-mediated toxicities: endocrinopathy, vitiligo, diarrhea, pneumonitis, transaminitis, hyperglycemia, and nephritis. Baseline tissue analysis on one of the responders showed sheets of cytotoxic T lymphocytes invading the tumor in a biopsy specimen. Responses to Nivo/Ipi in metastatic uveal melanoma are not confined to extrahepatic sites. In our study, 4 of 5 (80%) responses were seen in hepatic metastases. Durability of responses and impact on overall survival remain to be seen, and tissue-based exploratory correlative studies are under way. Citation Format: Michael Paul Shephard, Maura Glover, Gener Balmes, Suzanne Cain, Anna Vardeleon, Rosalind Mouton, Liberty Posada, Rinata Simien, Patrick Hwu, Michael Davies, Cassian Yee, Michael Wong, Hussein Tawbi, Scott Woodman, Rodabe Amaria, Adi Diab, Isabella Glitza, Wen-Jen Hwu, Sapna Patel. Clinical characteristics of responders to nivolumab plus ipilimumab (Nivo/Ipi) in metastatic uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A13.

A pilot study of nivolumab in combination with front-line neoadjuvant dose-dense paclitaxel and carboplatin chemotherapy in patients with high-grade serous ovarian cancer

Objective: In patients with epithelial ovarian cancer (EOC), increased intratumoral T cells are associated with a better prognosis, generating a rationale for combining chemotherapy with PD-1 blockade, such as nivolumab. In this study, we investigated the combination of nivolumab with neoadjuvant carboplatin and weekly paclitaxel for the upfront treatment of EOC. The primary objective was to measure safety and tolerability as determined by the rate of dose-limiting toxicities (DLTs). Secondary objectives included the complete gross resection rate (CGR), chemotherapy response score (CRS), progression-free survival (PFS), overall survival, and a range of translational parameters.

A multicenter randomized phase II study of nivolumab in combination with gemcitabine/cisplatin or ipilimumab as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-01).

4582 Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis with a median overall survival (OS) less than 12 months (mos). This randomized phase 2, multi-institutional, study was designed to investigate the role of combinational immunotherapy, using nivolumab (nivo) with gemcitabine (gem)/cisplatin (cis), or nivo with ipilimumab (ipi) in pts with untreated advanced BTC. Methods: Key eligibility criteria include histologically confirmed unresectable or metastatic BTC without prior systemic therapy, measurable disease per RECISTv1.1, ECOG PS 0-1, and absence of autoimmune disease or chronic steroid use. Arm A included gem 1000 mg/m2 and cis 25 mg/m2 d1, 8 Q3w + nivo 360 mg d1 Q3w for 6 mos followed by nivo 240 mg Q2w monotherapy for a total duration of 2 yrs; Arm B included nivo 240 mg Q2w and ipi 1 mg/kg Q6w for 2 yrs, in absence of disease progression. Primary endpoint is progression-free survival (PFS) rate at 6 mos with an alternative hypothesis of 80% (null hypothesis of 59%, one-sided alpha 0.05, power 80%) for each non-comparative arm. Secondary endpoints include overall response rate (ORR) per immune related (ir)RECIST, median PFS and OS and safety. Exploratory objectives include biomarker analysis using include sequential whole exome/transcriptome and immune cell subsets in tissue and blood. Results: 71 eligible pts (49% male, 83% Caucasian) with 35 in Arm and 36 in Arm B with a median age of 62 (range 20-80) yrs, and majority with metastatic disease (90%) were enrolled across 6 US sites. PFS rate at 6 mos was 70% in Arm A and 18.6% in Arm B. The median PFS was 8.8 mos (95% CI, 6.1 to 11.3) in Arm A and 4.1 mos (95% CI, 2.4-5.2) in Arm B. Ten patients on Arm A and 2 on Arm B remain on active treatment; additional 7 are in follow-up for OS. ORR, safety data and median OS evaluation are underway and will be presented at the meeting. Exploratory analyses are pending. Conclusions: The observed PFS rates at 6 mos in either arm are insufficient to reject the null hypothesis of 59% PFS at 6 months. While Arm B is inferior, Arm A appears to be as effective as standard of care although OS estimates are pending maturity. Clinical trial information: NCT03101566 .

NIVACOR: Phase II study of nivolumab in combination with FOLFOXIRI/bevacizumab in first-line chemotherapy for advanced colorectal cancer RASm/BRAFm patients.

TPS4118 Background: FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab has been shown to be one of the therapeutic regimens in first line with the highest activity profile in patients (pts) with metastatic colorectal cancer (mCRC) unselected for biomolecular alterations. Tumors co-opt the PD-1/PD-L1 signaling pathway as one key mechanism to evade immune destruction. Anti-PD-1 monoclonal antibodies are FDA approved only for DNA mismatch repair deficient/microsatellite instability-high (MMRd/MSI-H), which are only about 5% among all mCRC. Nowadays, there are no data demonstrating anti-PD1 activity in stable and proficient (MMRp/MSS) disease. Another critical therapeutic target is the Vascular Endothelial Growth Factor A (VEGF-A), which acts on endothelial cells to stimulate angiogenesis; his inhibition with bevacizumab increase immune cell infiltration, giving a strong rationale for combining VEGF targeted agents with immune checkpoint inhibitors. Based on evidence, we explore the combination of triplet chemotherapy (FOLFOXIRI) with bevacizumab and nivolumab in pts with mCRC all- RAS/BRAF mutant regardless of microsatellite status. Methods: This is a prospective, open-label, multicentric phase II trial where pts with mCRC RAS/BRAF mutant in first line will receive nivolumab in combination with FOLFOXIRI/Bevacizumab every 2 weeks for 8 cycles followed by maintenance with bevacizumab plus nivolumab every 2 weeks. Bevacizumab will be administered intravenously at dose of 5 mg/kg every 2 weeks and nivolumab intravenously as a flat dose of 240 mg every 2 weeks. The primary endpoint is the overall response rate (ORR) and our hypothesis is that the treatment is able to improve the ORR from 66% to 80%. Secondary endpoints include overall survival, safety, time to progression, duration of response. Collateral translational studies evaluate the tumor mutational burden, and genetic alterations by circulating free DNA (cfDNA) obtained from plasma samples. The trial is open to enrollment, 4 of planned 70 pts have been enrolled. Clinical trial information: EudraCT Number: 2018-002893-38. Clinical trial information: NCT04072198 .

Abstract OT2-04-07: Phase II study of nivolumab in combination with abemaciclib plus endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer (WJOG11418B, NEWFLAME trial)

Abstract Background: In this year, anti-programmed death-ligand 1 (PD-L1) antibody has been approved for PD-L1-positive metastatic triple-negative breast cancer by the U.S. Food and Drug Administration. The synergistic effect of the combination of anti-PD-L1 antibody, CDK4/6 inhibitor and endocrine therapy (ET) has been anticipated based on various preclinical data. A Phase Ib study (JPCE, NCT02779751) of abemaciclib plus pembrolizumab demonstrated manageable safety and promising anti-tumor activity in patients with HR-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC). Therefore, we initiated this investigator-initiated trial to evaluate the efficacy and safety of the combination of nivolumab, abemaciclib and ET (letrozole [LET] or fulvestrant [FUL]) as a first or second-line treatment in patients with HR+, HER2- MBC. Trial Design: This is a multicenter, multi-cohort, nonrandomized, open-label Phase II study to evaluate the efficacy and safety of nivolumab in combination with abemaciclib and ET (LET or FUL) in patients with HR+, HER2- MBC. Since there is no safety data of the combination of nivolumab, abemaciclib and ET, we evaluate safety and tolerability of the combination therapy in the first 6 patients with predefined dose-limiting toxicities. Patients will receive nivolumab 240 mg/body on day 1, 15, abemaciclib 150mg twice daily, and either LET 2.5mg once daily (LET cohort) or FUL 500mg on day1, day15 (FUL cohort) every 4 weeks until disease progression, unacceptable toxicity, or patient refusal. Pre- or perimenopausal women must receive concomitant treatment with a gonadotropin-releasing hormone agonist. Eligibility Criteria: Key eligibility criteria for the LET cohort are: postmenopausal HR+, HER2- MBC with ECOG PS≤1, measurable disease, no prior systemic therapy. ET in the adjuvant setting is permitted if the patient has a disease-free interval &amp;gt; 12 months from the completion of ET. Key eligibility criteria for the FUL cohort are: HR+, HER2- MBC with ECOG PS≤1, measurable disease, no more than one ET or any prior chemotherapy for MBC. Patients are required to have a disease that progressed while receiving adjuvant ET, ≤ 12 months after adjuvant ET, or while receiving ET for MBC. Specific Aims: The primary endpoint is the objective response rate (ORR) and key secondary endpoints include progression-free survival, overall survival, and the safety of the protocol treatment. Statistical Design: The threshold and expected ORR of LET cohort are 55% and 75%, respectively, and 16 patients are needed to ensure a statistical power of 80% (α=0.20). The threshold and expected ORR of FUL cohort are 45% and 60%, respectively, and 32 patients are needed to ensure a statistical power of 80% (α=0.20). Target Accrual: A total of 53 patients (LET cohort: 18, FUL cohort: 35) will be enrolled and duration of enrollment will be 1 year and 4 months. This trial opened to accrual in June 2019. Clinical trial information: JapicCTI-194782. Contact Information: Jun Masuda, Toranomon Hospital, Tokyo, Japan, masu-j@toranomon.gr.jp Citation Format: Jun Masuda, Junji Tsurutani, Norikazu Masuda, Manabu Futamura, Koji Matsumoto, Kenjiro Aogi, Masato Takahashi, Hiroji Iwata, Tsutomu Iwasa, Toru Mukohara, Kenichi Yoshimura, Takayuki Ueno, Toshimi Takano. Phase II study of nivolumab in combination with abemaciclib plus endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer (WJOG11418B, NEWFLAME trial) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-04-07.

Abstract P3-09-10: A phase II study of nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer (mTNBC)

Abstract Background: Patients (pts) with mTNBC have a poor prognosis, and new therapies are needed. Cabozantinib is a multikinase inhibitor that blocks VEGF receptor 2, reduces myeloid-derived suppressor cells, and increases T cell infiltration, suggesting it may enhance the activity of the anti-PD-1 checkpoint blockade agent nivolumab. Here, we report the safety and efficacy of nivolumab plus cabozantinib in a phase II single-arm study in mTNBC pts. Methods: Eligible pts had metastatic breast cancer that was estrogen and progesterone receptor &amp;lt; 10% and HER2 negative, measurable disease, and received 0-3 prior lines of chemotherapy in the advanced setting. Pts received nivolumab (480 mg intravenously on day 1, every 28 days) plus cabozantinib (40 mg daily by mouth). The primary endpoint was objective response rate (ORR) by RECIST v1.1. Using the Simons “optimal” method, if ≥ 3/18 pts responded during the first stage, 17 more would be enrolled. If ≥ 7/35 responded, the null hypothesis (ORR=10%) would be rejected in favor of a 30% ORR. Predefined secondary endpoints included progression free survival (PFS), clinical benefit rate (CBR), and toxicity. CBR was defined as the fraction of pts with any objective response or stable disease (SD) ≥ 24 weeks. Analyses associating PD-L1 expression, tumor-infiltrating lymphocytes (TIL), and genomic alterations (assessed by next generation sequencing on archival tissue) with outcomes were exploratory. Results: From 12/15/2017 to 01/24/2019, 18 pts were enrolled into the first stage of the trial; one partial response was seen (ORR 5.6%; 95% CI: 0.3-29.4), and the study was closed to further accrual. The median age was 58y, all pts had ECOG PS 0, and 7 (38.9%) had liver metastases. The median number of prior cytotoxic therapies for mTNBC pts was 1 (range 0 to 3). Three pts had SD ≥24 weeks and two had progressive disease best response. The CBR was 22.2%. After a median follow up of 3.7 months, the median PFS was 4.4 months (95% CI: 1.9-12.8), and the median OS was 6.9 months (95% CI: 3.4-NR). All-cause adverse events occurred in 100% of pts (G3-4, 78%) including elevated liver enzymes (any 50%; G3-4 16.7%), hand-foot syndrome (any 38.9%; G3-4 16.7%), fatigue (any 38.9%; G3-4 11.1%), and hypothyroidism (any 33.3%; no G3-4). Of the 9 pts with available genomic data, none had tumor mutational burden ≥ 10 mutations per megabase. Updated data with TIL, PD-L1, whole exome sequencing and RNA-sequencing results will be presented. Conclusions: The combination of nivolumab plus cabozantinib was not associated with any unexpected adverse events, however, with an ORR of 5.6%, the study did not achieve its primary endpoint. Exploratory genomic and immunological correlative studies are ongoing. Clinical trial information: NCT03316586. Citation Format: Romualdo Barroso-Sousa, Lorenzo Trippa, Tianyu Li, Tanya E Keenan, Grace Winship, Chelsea Andrews, Wafa Osmani, Beth Overmoyer, Eric P Winer, Elizabeth A Mittendorf, Dan G Duda, Sara M Tolaney. A phase II study of nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-10.

Phase IB/II Study of Nivolumab in Combination w Radium-223 in Men w Metastatic Castration Resistant Prostate Cancer

Phase IB/II Study of Nivolumab in Combination w Radium-223 in Men w Metastatic Castration Resistant Prostate Cancer

Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study

Outcomes for younger patients with acute myeloid leukaemia have moderately improved over the past two decades owing to better supportive care and recent introduction of novel targeted agents. Blocking PD-1 and its ligand's pathways enhances antileukaemia responses by enabling T cells in murine models. We aimed to assess the addition of nivolumab to frontline therapy with idarubicin and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome. This single-arm, phase 2 part of the phase 1-2 study of nivolumab in combination with idarubicin and cytarabine was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 18-60 years (or >60 years if suitable for intensive chemotherapy), and had newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome, and an Eastern Cooperative Oncology Group performance status of 0-2. Induction included cytarabine 1·5 g/m2 by 24-h continuous infusion daily on days 1-4 (3 days in patients >60 years) and idarubicin 12 mg/m2 daily on days 1-3. Nivolumab 3 mg/kg was started on day 24 (range 22-26) and continued every 2 weeks for up to a year in responders. Responders received either up to five consolidation cycles of attenuated doses of idarubicin and cytarabine, or allogeneic stem cell transplantation if eligible. The primary endpoint was event-free survival. Efficacy and safety analyses were done in all patients who received at least one dose of study treatment. Secondary endpoints were relapse-free survival and overall survival. This ongoing trial is registered with ClinicalTrials.gov, number NCT02464657. Between Aug 7, 2015, and June 2, 2018, 44 patients were enrolled of whom 22 (50%) had adverse genetic risk by European Leukaemia Network classification. All patients were evaluable for safety and efficacy. At a median follow-up of 17·25 months (IQR 0·50-30·40), median event-free survival was not reached (95% CI 7·93-NR). Median relapse-free survival of responders was 18·54 months (95% CI 8·20-23·22). The median overall survival was 18·54 months (95% CI 10·81-28·81). Six patients had seven grade 3-4 immune-related adverse events with two cases of rash, two of colitis, and one each of transaminitis, pancreatitis, and cholecystitis. 19 (43%) of 44 patients achieved a response and proceeded to allogeneic stem cell transplantation, with grade 3-4 graft-versus-host disease observed in five (26%). No treatment related deaths were attributed to nivolumab. Addition of nivolumab to induction chemotherapy with idarubicin and cytarabine is feasible in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome. Post-transplant severe graft-versus-host disease could be improved, and earlier initiation of checkpoint inhibitor therapy is warranted in future studies. The MD Anderson Cancer Center Support Grant CA016672, and the MD Anderson Cancer Center Leukaemia SPORE CA100632 from the National Cancer Institute, Bristol Myers Squibb.

A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular Carcinoma

A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular Carcinoma

Abstract CT088: Final results of the Phase I study of nivolumab in combination with CIMAvax, an epidermal growth factor(EGF)-depleting immunotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): Focus on biomarker analyses

Abstract BACKGROUND: The combination of nivolumab with CIMAvax is safe and can be administered together at the approved dosage of each agent administered as monotherapy. We report the analyses on circulating cytokines and putative biomarkers in relation to treatment outcomes. METHODS: Serial blood samples from 13 patients enrolled during dose-escalation were obtained and analyzed for dynamic changes in serum EGF and anti-EGF antibody (Ab) levels using ELISA-based assays. Circulating cytokines and relevant proteins implicated in EGF signaling were measured using Luminex multiplex bead array assays. Univariate analysis of variance was used to investigate the association between various analytes and treatment outcomes. Spearman rank correlation was calculated to determine the relationship between analytes. Tumor response was assessed using irRECIST and RECIST 1.1. RESULTS: 54% of enrolled pts had known tumor PD-L1 tumor proportion score (TPS) of 0%. Only 1 pt had PD-L1 TPS &amp;gt; 50%. Objective response rate was 31%, using either irRECIST or RECIST 1.1 criteria (3 pts PD-L1 TPS 0%, 1 pt PD-L1 TPS 60%). All enrolled pts had baseline serum EGF level &amp;gt; 250 pg/ml (mean 550, range 358 to 865) but there was no relationship between baseline EGF levels nor reduction in EGF level with tumor response. There was no difference between baseline levels of EGF-like ligands TGF-alpha, Neuregulin, Heparin-binding EGF according to tumor response. Excluding 2 pts who received less than 3 loading doses of CIMAvax, 82% of pts achieved good anti-EGF Ab titer &amp;gt; 1:4000 by day 43. Responders(R) had lower baseline neutrophil-lymphocyte ratio(NLR, OR 0.31, p=0.077). R had undetectable baseline levels of IFNa2 compared to nonR (mean 6.51 pg/ml, 95% CI 4.04-8.98). Baseline IL-7, IL-15 and CXCL11 levels in R were also lower compared to nonR (mean IL-7, 0.77 [95% CI, 0.54-1.0] vs 4.5 pg/ml [ 95% CI, 2.65 - 6.34]; mean IL-15, 0.95 [95% CI, 0.89-1.0) vs 5.50 pg/ml [95% CI, 3.07- 7.93]); mean CXCL11 20.75 [95% CI, 15.65 - 24.35] vs 87.87 pg/ml [95% CI, 20.38 - 155.37]), respectively. There is significant relationship between baseline levels of CXCL11 with NLR (r=0.59,p=.03)and C-reactive protein (CRP) levels (r=0.76, p=.002) and between CRP with NLR (r=0.71, p=0.006). CONCLUSIONS: Combination of nivolumab led to more pts achieving a good anti-EGF Ab titer earlier to CIMAVax (compared to historical cohort). Baseline EGF level is not associated with objective tumor response to the combination. Phase II portion of the study is ongoing. Citation Format: Grace K. Dy, Kelvin Lee, Adrienne Groman, Aileen Cinquino, Carlos Cedeno, Hans Minderman, Alan Hutson, Paul Wallace, Candace Johnson, Zaima Mazorra, Danay Saavedra Hernandez, Kalet Leon, Agustin Lage, Tania Crombet. Final results of the Phase I study of nivolumab in combination with CIMAvax, an epidermal growth factor(EGF)-depleting immunotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC): Focus on biomarker analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT088.

Translational Study of Nivolumab in Combination With Bevacizumab for Recurrent Glioblastoma

Translational Study of Nivolumab in Combination With Bevacizumab for Recurrent Glioblastoma