Dr Chahoud on the Rationale for Evaluating Zanzalintinib Plus Nivolumab With/Without Relatlimab in ccRCC

“STELLAR-002 is a phase [1], multiple-arm, dose escalation, dose expansion trial, trying to look at a new VEGF TKI, zanzalintinib, that has a shorter half-life, which usually helps a lot with the management of a lot of multi-TKI toxicities, in combination with nivolumab alone or in combination with relatlimab.”

Jad Chahoud, MD, MPH, an associate member in the Department of Genitourinary Oncology and medical director of IPOP at Moffitt Cancer Center, detailed the rationale for evaluating zanzalintinib (XL092) plus nivolumab (Opdivo) with or without relatlimab-rmbw (Opdualag) for the treatment of patients with previously untreated clear cell renal cell carcinoma (ccRCC).

The phase 1b STELLAR-002 trial (NCT05176483) evaluates the novel VEGF TKI, zanzalintinib, which has a shorter half-life and usually contributes toward the management of multi-TKI toxicities, Chahoud began. The regimen used in the study also includes nivolumab with or without relatlimab, he explained. Of note, many of the FDA-approved frontline therapies for ccRCC are a combination of immunotherapy plus VEGF TKIs or immunotherapy plus immunotherapy regimens, with no triplet regimens currently approved, he added.

The study includes patients at least 18 years of age with unresectable advanced or metastatic ccRCC who had not previously received systemic anticancer therapy for RCC. However, those who had previously received non-VEGF(R)–targeted adjuvant or neoadjuvant therapy are allowed on the study if disease recurrence occurred 6 months following the last dose. Additionally, patients from all IMDC risk groups are eligible. In the expansion cohort, patients are treated with either zanzalintinib at 100 mg daily plus nivolumab at 480 mg (n = 40) or zanzalintinib at the same dose level plus nivolumab at 480 mg and relatlimab at 480 mg every 4 weeks (n = 40).

The dual primary end points are safety and objective response rate per RECIST 1.1 criteria. The secondary end point is progression-free survival per RECIST 1.1 criteria.

At a median follow-up of 20.1 months (range, 17.7-26.7) in the doublet arm and 15.9 months (range, 11.3-17.3) in the triplet arm, reasons for discontinuation of all study treatment included radiographic progression (doublet, 33%; triplet, 23%), any treatment-emergent adverse effect (TEAE; 25%; 35%), AEs related to study treatment (8%; 20%), withdrawal of consent other than AE (3%; 3%), and physician decision (3%; 0%).