KEY TAKEAWAYS
- A Phase 3 clinical trial is investigating pembrolizumab plus lenvatinib with or without belzutifan and quavonlimab in patients with advanced ccRCC.
- The trial’s primary aim is to compare the efficacy and safety of three treatment arms in patients with metastatic ccRCC who have not previously received systemic treatment.
- Patients will be randomized to receive either pembrolizumab plus belzutifan and lenvatinib, MK-1308A plus lenvatinib, or pembrolizumab plus lenvatinib.
- The response will be evaluated using CT or MRI according to RECIST v1.1 by blinded independent central review.
- The trial’s main outcomes will be overall survival duration and time until disease progression.
- Secondary endpoints include patient-reported outcomes, safety, and objective response rates and duration according to RECIST v1.1.
In the phase 3 study KEYNOTE-581/CLEAR (NCT02811861), patients with advanced clear cell renal cell carcinoma (ccRCC) were treated with pembrolizumab plus the vascular endothelial growth factor (VEGF) inhibitor lenvatinib. In combination, the HIF-2 inhibitor belzutifan (MK-6482) and the CTLA-4 inhibitor quavonlimab (MK-1308A) exhibited anticancer effects in both ccRCC and non-small cell lung cancer. Combining HIF-2 or CTLA-4 inhibition with PD-1 and VEGF inhibition as first-line therapy in ccRCC may have additive benefits.
Pembrolizumab + belzutifan + lenvatinib (arm A) and MK-1308A + lenvatinib (arm B) will be compared against pembrolizumab + lenvatinib (arm C) in this open-label, randomized, phase 3 research (NCT04736706). There will be a total of about 1431 persons recruited who have metastatic ccRCC, have the detectable disease by RECIST v1.1, and have a Karnofsky Performance Status Scale score of 70% but have never received systemic treatment for advanced ccRCC. Each patient will receive either Arm A (belzutifan 120 mg + lenvatinib 20 mg orally once daily + pembrolizumab 400 mg IV every 6 weeks), Arm B (MK-1308A [quavonlimab 25 mg + pembrolizumab 400 mg] IV every 6 weeks and lenvatinib 20 mg oral once daily), or Arm C (pembrolizumab 400 mg IV every 6 weeks + lenvatinib 20 mg oral once daily). Patients will receive pembrolizumab plus MK-1308A for up to 18 cycles (about 2 years) until disease progression is confirmed, consent is withdrawn, or another treatment termination event occurs. Patients will be divided into three groups: those with good, fair, and poor International mRCC Database Consortium (IMDC) scores; those from North America, Western Europe, and the rest of the globe; and those with sarcomatoid traits. At week 12 post-randomization, every 6 weeks through week 78, and every 12 weeks afterward, the response will be evaluated by CT or MRI following RECIST v1.1 by blinded independent central review (BICR). Serious adverse events will be tracked for 90 days after treatment ends, and adverse events will be tracked throughout the research.
The two key end goals being studied are the survival time and time until disease progression as measured by BICR’s RECIST v1.1. Primary endpoints will be evaluated between Arms A and C, Arms B and C for patients with intermediate/poor IMDC status, and Arms A and C for all patients. Patient-reported outcomes, safety, and the rate and duration of objective responses according to RECIST v1.1 by BICR are secondary end goals.
Source: https://jitc.bmj.com/content/9/Suppl_2/A447
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT04736706
Toni Choueiri, Elizabeth Plimack, Thomas Powles, Martin Voss, Howard Gurney, Rachel Silverman, Rodolfo Perini, Karla Rodriguez-Lopez, Brian Rini/417 Phase 3 study of pembrolizumab + belzutifan + lenvatinib or pembrolizumab/quavonlimab + lenvatinib versus pembrolizumab + lenvatinib as first-line treatment for advanced renal cell carcinoma/Choueiri, T., Plimack, E., Powles, T., Voss, M., Gurney, H., Silverman, R., Perini, R., Rodriguez-Lopez, K., & Rini, B. (2021). 417 Phase 3 study of pembrolizumab + belzutifan + lenvatinib or pembrolizumab/quavonlimab + lenvatinib versus pembrolizumab + lenvatinib as first-line treatment for advanced renal cell carcinoma. Journal for ImmunoTherapy of Cancer, 9(Suppl 2), A447–A447. https://doi.org/10.1136/jitc-2021-sitc2021.417
