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| Ref Type | Journal Article | ||||||||||||
| PMID | (33323401) | ||||||||||||
| Authors | Zhou C, Wang Y, Zhao J, Chen G, Liu Z, Gu K, Huang M, He J, Chen J, Ma Z, Feng J, Shi J, Yu X, Cheng Y, Yao Y, Chen Y, Guo R, Lin X, Wang Z, Gao G, Wang Q, Li W, Yang X, Wu L, Zhang J, Ren S | ||||||||||||
| Title | Efficacy and Biomarker Analysis of Camrelizumab in Combination with Apatinib in Patients with Advanced Nonsquamous NSCLC Previously Treated with Chemotherapy. | ||||||||||||
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| Abstract Text | Our preclinical work suggests that appropriate angiogenesis inhibition could potentiate PD-1/PD-L1 blockade via alleviating hypoxia, increasing infiltration of CD8 + T cells and reducing recruitment of tumor-associated macrophages. We hereby conducted a clinical trial to evaluate this combination in pretreated patients with advanced non-small cell lung cancer (NSCLC). The study included phase Ib apatinib dose-escalation and phase II expansion cohorts. Patients received apatinib at doses of 250-500 mg orally once daily, in combination with camrelizumab 200 mg intravenously every 2 weeks. From March 2017 to October 2018, 105 chemotherapy-pretreated patients with nonsquamous NSCLC were enrolled and received apatinib 250 mg (recommended phase II dose) and camrelizumab. Among them, one (1.0%) complete response, 28 (26.7%) partial responses, and 48 (45.7%) stable diseases were observed. In the efficacy-evaluable population ( n = 94), objective response rate (ORR) was 30.9% [95% confidence interval (CI), 21.7-41.2]. The median progression-free survival was 5.7 months (95% CI, 4.5-8.8) and overall survival was 15.5 months (95% CI, 10.9-24.5). Efficacy of combination therapy was evident across all PD-L1 and tumor mutation burden subgroups, and appeared to be improved in patients with STK11/KEAP1 mutation (mutant vs. wild-type, ORR: 42.9% vs. 28.1%; 1-year survival rate: 85.1% vs. 53.1%). No unexpected adverse events were observed. Combined apatinib and camrelizumab showed encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced nonsquamous NSCLC. Patients with STK11/KEAP1 mutation might derive more benefits from this combination. We will validate these results in an ongoing phase III trial (NCT04203485). | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| STK11 mutant | lung non-squamous non-small cell carcinoma | predicted - sensitive | Camrelizumab + Rivoceranib | Phase Ib/II | Emerging | In a Phase Ib/II trial, non-squamous NSCLC patients harboring STK11 and/or KEAP1 mutations (n=14) demonstrated an improved 12-month survival rate (85.1% vs 53.1%; p=0.01), and a trend towards improved objective response rate (42.9% vs 28.1%; p=0.33), disease control rate (92.9% vs 65.6%, p=0.053), and median progression-free survival (9.4 vs 5.3 months; p=0.64) compared to wild-type STK11/KEAP1 patients (n=32) treated with Camrelizumab (SHR-1210) plus Rivoceranib (apatinib) (PMID: 33323401; NCT03083041). | 33323401 |
| KEAP1 mutant | lung non-squamous non-small cell carcinoma | predicted - sensitive | Camrelizumab + Rivoceranib | Phase Ib/II | Emerging | In a Phase Ib/II trial, non-squamous NSCLC patients harboring KEAP1 and/or STK11 mutations (n=14) demonstrated an improved 12-month survival rate (85.1% vs 53.1%; p=0.01), and a trend towards improved objective response rate (42.9% vs 28.1%; p=0.33), disease control rate (92.9% vs 65.6%, p=0.053), and median progression-free survival (9.4 vs 5.3 months; p=0.64) compared to wild-type KEAP1/STK11 patients (n=32) treated with Camrelizumab (SHR-1210) plus Rivoceranib (apatinib) (PMID: 33323401; NCT03083041). | 33323401 |
| CD274 positive | lung non-squamous non-small cell carcinoma | not predictive | Camrelizumab + Rivoceranib | Phase Ib/II | Actionable | In a Phase Ib/II trial, combined Camrelizumab (SHR-1210) and Rivoceranib (apatinib) treatment in patients with CD274 (PD-L1)-positive (TPS>=1%; n=25) non-squamous non-small cell lung cancer resulted in a similar objective response rate (36.0%, 9/25 vs 22.7%, 15/66; p=0.20), disease control rate (72.0%,18/25 vs 71.2%, 47/66; p=0.94), and median progression-free survival (6.8 vs 5.1 months; p=0.29) to patients with CD274 (PD-L1)-negative (TPS<1%; n=66) tumors (PMID: 33323401; NCT03083041). | 33323401 |