OA04.03 A Randomized Phase 3 Study of Camrelizumab plus Chemotherapy as 1st Line Therapy for Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer

Abstract

low-dose ipilimumab in advanced NSCLC. Here we evaluate this regimen as first-line treatment in special populations (cohort A1) and a reference population (cohort A; previously reported). Method: Patients had previously untreated advanced NSCLC. Cohort A1 (n¼198) had ECOG PS 2 or ECOG PS 0e1 with 1 of: asymptomatic untreated brain metastases, hepatic or renal impairment, or HIV. Cohort A (n¼391) had ECOG PS 0e1. Patients with known EGFR mutations or ALK translocations sensitive to available targeted therapy were excluded from both cohorts. Nivolumab 240 mg Q2W plus ipilimumab 1 mg/kg Q6W was administered for two years or until disease progression/unacceptable toxicity. Safety and efficacy endpoints were assessed; cohort A1 analyses were exploratory. Result: Cohort A1 patients were grouped as: ECOG PS 2 (n¼139) and all other special populations (AOSP; n¼59). Baseline characteristics were generally balanced between cohorts. Rates of grade 3e4 treatment-related adverse events (TRAEs) were similar between cohorts; within cohort A1, grade 3e4 TRAEs were numerically higher in AOSP versus the ECOG PS 2 subgroup; TRAEs leading to discontinuation were similar across populations (Table). ORR was 25% in cohort A1 (patients with ECOG PS 2, 20%; AOSP, 37%) and 35% in cohort A. PFS was numerically shorter in cohort A1 than cohort A; high TMB (10 mut/Mb) and higher PD-L1 expression (1% or 50%) were associated with numerically longer PFS in both cohorts (Table). Conclusion: First-line flat-dose nivolumab plus weight-based ipilimumab showed a consistent safety profile in special populations with advanced NSCLC, including those with ECOG PS 2. Patients with either high TMB or higher tumor PD-L1 expression appeared to exhibit improved efficacy.

The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers

“…After carefully screening the full text or conference abstracts, 24 articles were eligible. Finally, 15 articles with 1,390 patients were included after removing nine articles with duplicate data (Fang et al, 2018;Huang et al, 2019a;Huang et al, 2019b;Liu et al, 2019;Qin et al, 2019;Shen et al, 2019;Wu et al, 2019;Xie et al, 2019;Xu et al, 2019;Zhang et al, 2019;Zhou et al, 2019a;Zhou et al, 2019b;Chen et al, 2020a;Lickliter et al, 2020;Qin et al, 2020). Trial NCT03121716 had both a single-agent cohort (camrelizumab alone) and a combination cohort (camrelizumab plus other therapies), and the two cohorts were enrolled separately as two studies (Fang et al, 2018).…”

Camrelizumab Combined with FOLFOX4 Regimen as First-Line Therapy for Advanced Hepatocellular Carcinomas: A Sub-Cohort of a Multicenter Phase Ib/II Study

“…Our results are similar to the incidence of hematological toxicity of camrelizumab in combination with chemotherapy for other cancer varieties. 27,30 RCCEP was the most common TRAE of camrelizumab, with an incidence as high as 73.5% in this study, but all cases were grade 1-2 and were mainly distributed on the skin surface, which recovered spontaneously after drug withdrawal. Notably, this TRAE was positively correlated with ORR, 39 and its specific mechanism and value in predicting efficacy require confirmation in further studies.…”

“…There have been no reports of immunotherapy in combination with systemic chemotherapy for HCC treatment, but this treatment paradigm has shown superior efficacy to monotherapy in a variety of other solid tumors, such as NSCLC and nasopharyngeal carcinoma. [24][25][26][27][28][29][30] Systemic chemotherapy can inhibit and kill tumor cells, releasing a large number of T cell chemokines after exposure to antigens and leading to T cell accumulation around the tumor, which is then exploited by immunotherapy; therefore, this combination therapy can control tumor development, gaining time for immunotherapy to response and synergizing the treatment effects. [31][32][33] Some chemotherapeutic drugs, represented by oxaliplatin, enhance the immune response of tumor cells by inducing immunogenic cell death (ICD), 31 acting on cellular signal transducer and activator of transcription (STAT) protein signaling pathways, 34 and regulating the tumor microenvironment.…”

Identifying optimal first-line interventions for advanced non-small cell lung carcinoma according to PD-L1 expression: a systematic review and network meta-analysis

“…Their findings suggest that Camrelizumab plus chemotherapy may result in a substantial clinical benefit for those diagnosed with advanced non-squamous NSCLC and with negative oncogenic drivers, in terms of PFS, ORR and OS. 24 This combination may become an approved first-line therapy, although, further clinical research is required because our forthcoming network meta-analysis of PD-L1-high patients, appears to suggest that Camrelizumab plus chemotherapy maybe inferior to both ABC and PC, and appears only marginally superior to both Pembrolizumab alone, and AC (data not provided here).…”