KEYNOTE-427 Updated Results from Cohort A

Researchers reported updated results from cohort A in the KEYNOTE-427 trial during a poster session at the ASCO 2019 Annual Meeting. KEYNOTE-427 is an open-label, single-arm, phase d2 study designed to examine efficacy and safety of first-line single-agent pembrolizumab in patients with clear cell renal cell carcinoma (ccRCC)  (cohort A) and in patients with non–clear cell RCC (cohort B). Pembrolizumab is a programmed death 1 (PD-1) inhibitor.

Scott S. Tykodi, MD, and colleagues reported the updated results in a poster titled First-line Pembrolizumab (pembro) Monotherapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Results for KEYNOTE-427 cohort A.

Patients in cohort A had histologically confirmed ccRCC, measured by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1), and no prior systemic therapy. Study participants received pembrolizumab 200 mg intravenously for 2 years or until confirmed progressive disease, unacceptable toxicity, or patient decision to withdraw.

The primary end point of interest was objective response rate per RECIST v1.1 blinded independent central review. Secondary end points included duration of response, disease control rate, progression-free survival, overall survival, and safety.

Median age of the 110 patients in cohort A was 64 years and median follow-up was 18.0 months. Among the 110 patients, 38.2% had favorable International Metastatic RCC Database Consortium (IMDC) risk, 47.3% had intermediate risk, and 14.5%^ had poor risk. Forty-seven point three percent were PD-L1 positive.

Confirmed objective response rate was 36.4% with three patients (2.7%) with complete response and 37 (33.6%) with partial response. Median duration of response was not reached; median progression-free survival was 7.1 months (95% confidence interval; 5.6%-11.0%); median overall survival was not reached.

Among the patients with IMDC favorable risk (n=42), objective response rate was 31.0% (95% CI, 17.6%-47.1%); disease control rate was 61.9% (95% CI, 45.6%-76.4%); median duration of response was 13.7 months (95% CI, 4.2 months-18.0 months); and duration of response ≥6 months among responders was 68.4%. Among those with intermediate/poor IMDC risk, the values were 39.7% (28.0%-52.3%); 54.4% (41.9%-66.5%); not reached; and 80.9%, respectively.

As measured by PD-L1 status, confirmed objective response rate was 44.2% and 29l.3% for positive and negative, respectively. By sarcomatoid differentiation (n=11), confirmed objective response rate was 63.6%.

Treatment-related adverse events occurred in 80.9% of patients; pruritus and fatigue were the most commonly reported AEs (28.2% for both). One patient died of treatment-related pneumonitis.

In conclusion, the researchers said, “With a median 18 months follow-up, first-line pembro monotherapy continued to show antitumor activity in patients with ccRCC. Meaningful responses were observed in patients with intermediate/poor IMDC risk, PD-L1 positive, and sacromotoid differentiated tumors. Safety profile was comparable to previously reported.”

Clinical trial information: NCT02853344

Source: Tykodi SS, Donskov F, Lee J-L; et al. First-line pembrolizumab (pembro) monotherapy in advanced clear cell renal cell carcinoma (ccRCC): Updated results for KEYNOTE-427 cohort A. Abstract of a poster presented at the American Society of Clinical Oncology 2019 Annual Meeting, June 3, 2019, Chicago, Illinois.