Article ; Online: A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non-Small Cell Lung Cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research
2021 Volume 27, Issue 13, Page(s) 3630–3640
Abstract: Purpose: The CLASSICAL-Lung clinical trial tested the combination of pepinemab, an IgG4 humanized mAb targeting semaphorin 4D, with the PD-L1 inhibitor avelumab to assess the effects of coupling increased T-cell infiltration and reversal of immune ... ...
| Abstract | Purpose: The CLASSICAL-Lung clinical trial tested the combination of pepinemab, an IgG4 humanized mAb targeting semaphorin 4D, with the PD-L1 inhibitor avelumab to assess the effects of coupling increased T-cell infiltration and reversal of immune suppression via pepinemab with sustained T-cell activation via checkpoint inhibition. Patients and methods: This phase Ib/II, single-arm study was designed to evaluate the safety, tolerability, and efficacy of pepinemab in combination with avelumab in 62 patients with advanced non-small cell lung cancer (NSCLC), including immunotherapy-naïve (ION) patients and patients whose tumors progressed following anti-PD-1/L1 monotherapy (IOF). The main objectives were to evaluate safety/tolerability, establish a recommended phase 2 dose (RP2D), obtain a preliminary evaluation of antitumor activity, and investigate candidate biomarker activity. Results: The combination was well tolerated with no major safety signals identified. Pepinemab, 10 mg/kg with avelumab, 10 mg/kg, every 2 weeks, was selected as the RP2D. Among 21 evaluable ION patients, 5 patients experienced partial responses (PR), 4 patients evidenced clinical benefit ≥1 year, and the disease control rate (DCR) was 81%. Notably, overall response rate with the combination therapy was higher than previously reported for single-agent avelumab in the PD-L1-negative/low population. Among 29 evaluable IOF patients, the combination resulted in a DCR of 59%, including 2 PR and 7 patients with durable clinical benefit of ≥23 weeks. Biomarker analysis of biopsies demonstrated increased CD8 T-cell density correlating with RECIST response criteria. Conclusions: The combination of pepinemab with avelumab was well tolerated in NSCLC and showed signs of antitumor activity in immunotherapy-resistant and PD-L1-negative/low tumors. |
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| MeSH term(s) | Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Agents, Immunological/administration & dosage ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Neoplasm Staging | |||||
| Chemical Substances | Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Immunological ; avelumab (KXG2PJ551I) ; pepinemab | |||||
| Language | English | |||||
| Publishing date | 2021-04-05 | |||||
| Publishing country | United States | |||||
| Document type | Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 1225457-5 | |||||
| ISSN | 1557-3265 ; 1078-0432 | |||||
| ISSN (online) | 1557-3265 | |||||
| ISSN | 1078-0432 | |||||
| DOI | 10.1158/1078-0432.CCR-20-4792 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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