木瓜直播

An investigational combination of CTLA-4 and PD‐1 checkpoint inhibitors demonstrated "encouraging" tumor activity, as well as a manageable safety profile, in patients with advanced/metastatic solid tumors, according to results from a small phase I study.

Among 61 patients with different solid tumors who were evaluated for efficacy, 37.7% achieved an objective response to treatment with the anti-CTLA‐4 human immunoglobulin (Ig) G1 monoclonal antibody CS1002 and the anti-PD‐1 humanized recombinant IgG4 monoclonal antibody CS1003 (also known as nofazinlimab), reported Sarwan Bishnoi, MD, of the University of Adelaide in Australia, and colleagues.

In the 92 patients evaluated for safety, no dose‐limiting toxicities or maximum tolerated doses were observed, they noted in .

"Combination therapy with anti-CTLA‐4 and anti-PD‐(L)1 antibodies was recently approved for patients with advanced melanoma, high/intermediate‐risk renal cell carcinoma, non-small cell lung cancer, mesothelioma, and advanced high microsatellite instability/mismatch repair deficient (MSI‐H/dMMR) colorectal cancer, underscoring the therapeutic potential of this regimen," Bishnoi and team wrote. "Anti-CTLA‐4 plus anti-PD(L)‐1 therapy has also exhibited promising activity in patients with anti-PD(L)‐1‐antibody refractory tumors, including melanoma and hepatocellular carcinoma (HCC)."

This , conducted from April 2018 to January 2022 at nine study sites in Australia and China, consisted of three parts: a phase Ia monotherapy dose escalation with CS1002 (part 1, n=13), a phase Ib combination therapy dose escalation (part 2, n=18), and expansion (part 3, n=61).

The dose‐escalation portion included patients with advanced/metastatic solid, relapsed, or refractory tumors, while the dose‐expansion portion included patients with immunotherapy‐naive or immunotherapy‐refractory advanced/metastatic tumor types.

In Part 3, the best overall response assessed by the investigator was complete response for four patients (6.6%), partial response for 19 patients (31.1%), stable disease for 14 patients (23%), and progressive disease for 18 patients (29.5%).

The objective response rate was 54.5% in patients with MSI-H/dMMR tumors, 28.6% in those with melanoma, and 7.1% in those with HCC.

Higher objective response rates were observed with conventional and high‐dose CS1002 regimens (1 mg/kg every 3 weeks or 3 mg/kg every 9 weeks) compared with low‐dose CS1002 (0.3 mg/kg every 3 weeks) in MSI‐H/dMMR tumors (50% vs 58.8%), melanoma (14.3% vs 42.9%), and HCC (0% vs 16.7%), "suggesting dose‐dependent efficacy, especially in patients with anti-PD(L)1‐refractory tumors," the authors wrote.

Data on duration of response were not mature among patients with MSI‐H/dMMR tumors, melanoma, or HCC. However, the objective responses observed in part 3 "were considered durable," Bishnoi and team added, with 60.9% of responses lasting for at least 6 months.

Treatment‐related adverse events (TRAEs) such as diarrhea, fatigue, and rash were reported in 30.8%, 83.3%, and 75% of patients in parts 1, 2, and 3, respectively, while grade ≥3 TRAEs such as intestinal inflammation and severe skin reactions were reported by 15.4%, 50%, and 18.3%, respectively.

Bishnoi and colleagues acknowledged that while there were limitations to the study, particularly the small number of HCC patients, "the observed response is encouraging, and further clinical development of this regimen is warranted."

Comment