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Clinical Trial
. 2023 Nov 21;4(11):101242.
doi: 10.1016/j.xcrm.2023.101242. Epub 2023 Oct 17.

A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors

Sophia Frentzas  1 , Hui K Gan  2 , Rasha Cosman  3 , Jermaine Coward  4 , Ben Tran  5 , Michael Millward  6 , Yiting Zhou  7 , Wenjing Wang  7 , Dennis Xia  7 , Zhongmin Maxwell Wang  7 , Baiyong Li  7 , Michelle Xia  7 , Jayesh Desai  8
Affiliations
Clinical Trial

A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors

Sophia Frentzas et al. Cell Rep Med. .

Abstract

Simultaneous inhibition of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) with bispecific antibodies may improve efficacy over single-agent treatment while limiting toxicity. Cadonilimab is a humanized, bispecific antibody targeting PD-1 and CTLA-4. This is a phase 1 study of cadonilimab including dose escalation (n = 39) and dose expansion (n = 80). One dose-limiting toxicity event is observed, with the maximum tolerated dose not reached. 6 mg/kg cadonilimab once every 2 weeks is established as the recommended dose for future studies. The most common treatment-related adverse event is infusion-related reaction (18.5%), mostly grade 1/2 in severity. The incidences of any grade and grade ≥3 immune-related adverse events are 44.5% and 6.7%, respectively. The confirmed overall response rate is 13.4%, and the median duration of response is 12.9 months. Cadonilimab is well tolerated and showed promising efficacy in patients with advanced solid tumors. This study is registered with ClinicalTrials.gov: NCT03261011.

Keywords: CTLA-4; PD-1; advanced solid tumors; bispecific antibody; cadonilimab; immune checkpoint inhibitor.

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Conflict of interest statement

Declaration of interests S.F. has received research funding and honoraria from Amgen; has consulted and advised for Akeso Biopharma and Merck Sharpe and Dohme (MSD); and has received support from Amgen for attending meetings and/or travel and industry trial sponsorship to study site (principal investigator of multiple studies) from Akeso Biopharma, Ambrax, Amgen, AstraZeneca, Aulos, Bristol-Myers Squibb (BMS), BeiGene, Cullinan, Daiichi Sankyo, Edison Oncology, MSD, Pfizer, Takeda, HaiHe Biopharma, Vivace, and WMS. H.K.G. has consulted/advised for BMS, Curis, Merck Serono, and Telix. B.T. has received research funding from Amgen, Astellas, AstraZeneca, Bayer, BMS, Genentech, Ipsen, Janssen, Pfizer, Movember, and MSD; has received honoraria from Amgen, Astellas, AstraZeneca, Bayer, BMS, Ipsen, Janssen, Merck, MSD, Pfizer, Sanofi, and Tolmar; and has served in a consulting/advisory role for Amgen, Astellas, AstraZeneca, Bayer, BMS, Ipsen, IQVIA, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, and Tolmar. M.M. has received research funding from BMS and honoraria from BMS, Roche, and the Limbic; has consulted/advised for MSD, the Limbic, Roche, BMS, Takeda, Guardant Health, BeiGene Australia, Amgen, Merck, Lilly, and Novartis; and has received support for attending meetings and/or travel from AstraZeneca. Y.Z., W.W., D.X., M.W., B.L., and M.X. are employees of Akeso Biopharma. J.D. has received institutional research funding from Amgen, AstraZeneca, BeiGene,BMS, GlaxoSmithKline, Roche/Genentech, and Eli Lilly and has consulted/advised for Pierre Fabre, Pfizer, Lilly, Merck KGaA, Roche, Boehringer Ingelheim, Novartis, Antengene, and BeiGene.

Figures

None
Graphical abstract
Figure 1
Figure 1
Study flow diagram aOne patient experienced grade 3 infusion-related reaction during the second dose, which resolved within 6 h; this patient was replaced, as she failed to receive >90% of the cadonilimab dose within the first cycle. Although this was not deemed as a dose-limiting toxicity (DLT) event, it was considered of clinical significance and thus included in the DLT-evaluable set per the Dose Escalation Committee agreement. bIncludes one DLT non-evaluable patient. cDose-expansion cohort II enrolled patients who had previously received ICI treatment. For other dose escalation and expansion cohorts, there was no specific requirement regarding prior ICI use. Q2W, once every 2 weeks; Q3W, once every 3 weeks.
Figure 2
Figure 2
Tumor response (A) Waterfall plot of best overall response in all patients. (B) Tumor responses in responding patients. (C) Radiological images of target lesion over time in a patient with lung large-cell neuroendocrine carcinoma who achieved CR. CR, complete response; CRC, colorectal cancer; ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; LCNEC, large-cell neuroendocrine carcinoma; m, month; MSI, microsatellite instability; MSI-H, high microsatellite instability; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; Q2W, once every 2 weeks; Q3W, once every 3 weeks; RCC, renal cell carcinoma; SCC, squamous cell carcinoma; TNBC, triple-negative breast cancer.
Figure 3
Figure 3
Tumor response in patients with mesothelioma (A) Waterfall plot of best overall response in patients with mesothelioma. (B) Swimmer plot of treatment duration in patients with mesothelioma. NA, not available; PD, progressive disease; PR, partial response; Q2W, once every 2 weeks; Q3W, once every 3 weeks; SD, stable disease.
See this image and copyright information in PMC

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