A phase 1 study is investigating anti-TIGIT therapy combined with immune checkpoint inhibition for the patients with metastatic microsatellite stable colorectal cancer.
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The first patient with metastatic microsatellite stable colorectal cancer (MSS-CRC) has been dosed with the best-in-class anti-TIGIT antibody, COM902, combined with COM701 and pembrolizumab (Keytruda) in a proof-of-concept study of patients with advanced malignancies (NCT04354246).1
As previously reported by Targeted Oncology ™, COM902 monotherapy first demonstrated in vitro activity that was comparable to other anti-TIGIT therapies that are in clinical development.2 Research also shows that COM902 binds to human, cynomolgus monkey, and mouse TIGIT, and disrupts the binding of TIGIT with the poliovirus receptor (PVR).3
Trial Name: A Phase 1 Study of The Safety and Tolerability of COM902 in Subjects With Advanced Malignancies
ClinicalTrials.gov Identifier: NCT04354246
Sponsor: Compugen Ltd
Recruitment Contact: +1 415 373 0781, COM902-001@cgen.com
Completion Date: September 30, 2023
"Treatment options are limited for patients with metastatic microsatellite stable colorectal cancer who have exhausted standard of care, and in particular for the majority of patients who also have liver metastases," said Manish Sharma, MD, associate director of Clinical Research at START Midwest in Grand Rapids, Michigan. "I am very excited to have dosed the first patient in this proof-of-concept study with the novel triple combination of COM701, COM902, and pembrolizumab which I hope will bring new treatment options for patients with MSS CRC."
The study comes on the heels of phase 1 cohort expansion data (NCT03667716) that was presented at the Society of Immunotherapy for Cancer (SITC) Annual Meeting 2022. In the study, COM701 was combined with nivolumab (Opdivo) for the treatment of 22 patients with previously-treated MSS-CRC.
COM701 plus nivolumab showed anti-tumor activity with an objective response rate (ORR) of 9% in the overall population. Among 17 patients with liver metastases, the ORR was 12%. All responses were partial responses. The disease control rate was 27%. No new safety signals were revealed in this study.
The ongoing study of COM902 with COM701 and pembrolizumab is enrolling patients who had been previously treated with up to 3 lines of therapy at sites in Michigan, Ohio, Tennessee, and Texas. Patients with a histologically or cytologically confirmed diagnosis of an advanced malignancy, who have no other treatment option, and are not candidates for standard therapy are eligible to enroll if they present with an ECOG performance status of 0 or 1.
The study excludes patients who have received prior treatment with a TIGIT inhibitor, have symptomatic interstitial lung disease or inflammatory pneumonitis or have a history of immune-related adverse events that caused them to discontinue treatment with an immunotherapy agent.
"The goal of the study is to build on the encouraging data previously reported at the annual meeting of the Society for Immunotherapy of Cancer 2022, with the dual blockade of PVRIG and PD-1; [the data] help us better understand the contribution of the components, and build on the biomarker work we are doing to try and identify the patients most likely to respond, with the purpose of building a path to registration,” said Anat Cohen-Dayag, PhD, president, and chief executive officer of Compugen, in the press release.
REFERENCES:
1. Compugen doses first patient in triple combination COM701, COM902 and pembrolizumab MSS CRC proof-of-concept study. News release. Compugen Ltd. March 6, 2023. Accessed March 7, 2023. https://bit.ly/3YsikmA
2. Hansen K, Kumat S, Logronio K, et al. COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade. Cancer Immunol Immunother. 2021;70(12):3525-3540. doi: 10.1007/s00262-021-02921-8.
3. Rasco D, Dumbrava E, Sharma M, et al. 659 COM701 plus nivolumab demonstrates preliminary antitumor activity and immune modulation of tumor microenvironment in patients with metastatic MSS-CRC and liver metastases. J Immunother Cancer. 2022;10. doi: 10.1136/jitc-2022-SITC2022.0659
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