Cadonilimab for PD-1/PD-L1 Blockade-refractory, MSI-H/dMMR, Advanced Colorectal Cancer
Status:
Not yet recruiting
Trial end date:
2027-07-01
Target enrollment:
Participant gender:
Summary
KEYNOTE-177 is currently the only randomized controlled phase III clinical trial evaluating
the efficacy and safety of pembrolizumab versus standard chemotherapy combined with targeted
first-line therapy for dMMR/MSI-H metastatic colorectal cancer. The study was conducted at
192 centers in 23 countries and enrolled a total of 307 subjects. The results of the study
showed that the median PFS of pembrolizumab was 16.5 months, which was double the 8.2 months
in the chemotherapy group (HR 0.60; 95% CI: 0.45-0.80; P = 0.0002). In addition, the ORR was
45.1% in the pembrolizumab group and 33.1% in the chemotherapy group, and a higher percentage
of patients achieving a complete remission (CR) with pembrolizumab than in the chemotherapy
group (13.1% vs. 3.9%). The U.S. FDA approved pembrolizumab in June 2020 for the first-line
treatment of MSI-H/dMMR metastatic colorectal cancer.
The results of the KEYNOTE-177 study showed that 29% of patients with dMMR/MSI-H metastatic
colorectal cancer experienced direct disease progression (PD) after first-line pembrolizumab
monotherapy. This may suggest that some dMMR/MSI-H patients have primary resistance to
anti-PD-1 monotherapy. In the first-line treatment cohort of the CheckMate 142 study using
nivolumab combined with ipilimumab, the proportion of patients with direct PD was 13%,
suggesting that the combination of PD-1 inhibitors and anti-CTLA-4 mAb may have help overcome
this primary resistance. In addition, in the second-line and above cohort of the CheckMate142
study, 12% of patients receiving nivolumab in combination with ipilimumab experienced PD
directly, compared with 26% of patients receiving nivolumab alone.
A study published on 《The Lancet Oncolog》 on the efficacy and safety of ipilimumab
monotherapy and ipilimumab combined with anti-PD-1 monoclonal antibody in patients with
anti-PD-1 monoclonal antibody-resistant melanoma Retrospective study. The study included 355
patients with unresectable metastatic stage III or IV melanoma who received ipilimumab
monotherapy after failure of anti-PD-(L)1 monoclonal antibody (n=162), or Ipilimumab combined
with anti-PD-1 therapy (n=193). The ORR was 31% in the combination arm, significantly higher
than the 13% in the ipilimumab monotherapy arm. In addition, the median OS and PFS of the
combination therapy group were 20.4 months and 3.0 months, respectively, which were also
significantly higher than those of the single-agent group of 8.8 months and 2.6 months.
The aim of this study was to evaluate the objective response rate (ORR) of Cadonilimab, a
bispecific anti-PD-1/CTLA-4 antibody, for PD-1/PD-L1 blockade-refractory, microsatellite
instability-high (MSI-H) or mismatch repair-deficient (dMMR), advanced colorectal cancer.