Belzutifan plus zanzalintinib versus belzutifan alone for advanced renal cell carcinoma
A Phase 3, Randomized, Double-blind, Study of Belzutifan + Zanzalintinib Versus Belzutifan + Placebo in Participants With Advanced RCC Who Have Progressed on or After Both PD-1/L1 and VEGF-TKI Therapies in Sequence or in Combination (LITESPARK-034)
This trial tests whether adding the targeted drug zanzalintinib to belzutifan helps people with advanced renal cell carcinoma live longer and delay tumor growth compared with belzutifan plus placebo.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 758 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Merck Sharp & Dohme LLC Industry-sponsored |
| Drugs / interventions | zanzalintinib |
| Locations | 7 sites (Río Cuarto, Córdoba Province and 6 other locations) |
| Trial ID | NCT07489495 on ClinicalTrials.gov |
What this trial studies
This randomized Phase 3 trial compares belzutifan combined with zanzalintinib to belzutifan plus placebo in people with unresectable, advanced renal cell carcinoma that has a clear-cell component. Eligible participants must have measurable disease and may have received up to three prior systemic therapies, including no more than one prior PD-1/PD-L1 inhibitor. The co-primary goals are to compare overall survival and time without disease worsening (progression-free survival) between the two treatment arms. The multicenter international study is sponsored by Merck Sharp & Dohme with collaboration from Exelixis and is open at sites in countries including Argentina and Australia.
Who should consider this trial
Good fit: Ideal candidates have unresectable, advanced clear-cell renal cell carcinoma with measurable disease, have had no more than three prior systemic regimens (including only one prior PD-1/PD-L1 therapy), and meet standard safety criteria for investigational targeted therapies.
Not a fit: Patients without a clear-cell component, those who require chronic supplemental oxygen, have recent significant cardiovascular disease, or many prior lines of therapy may be unlikely to benefit or may be excluded from the study.
Why it matters
Potential benefit: If successful, adding zanzalintinib to belzutifan could help people with advanced RCC live longer and keep their cancer under control for a longer time.
How similar studies have performed: Belzutifan has shown activity in RCC and combinations of targeted agents have improved outcomes in some prior RCC settings, but combining belzutifan with zanzalintinib is a new approach being tested in this Phase 3 trial.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition) * Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) * Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy Exclusion Criteria: For exclusion criteria: The main exclusion criteria include but are not limited to the following: * Has any of the following: a pulse oximeter reading \<92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen * Has clinically significant cardiovascular disease within 12 months from first dose of study intervention * Has deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization * Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram * Has had major surgery within 8 weeks before randomization * Has current pneumonitis/interstitial lung disease * Has a history of human immunodeficiency virus infection * Has Hepatitis B or Hepatitis C virus infection * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has a history of solid organ transplant * Has not adequately recovered from major surgery or has ongoing surgical complications
Where this trial is running
Río Cuarto, Córdoba Province and 6 other locations
- Centro Privado de RMI Río Cuarto S.A. II ( Site 0255) — Río Cuarto, Córdoba Province, Argentina (Recruiting)
- Centro Oncológico Riojano Integral ( Site 0256) — La Rioja, Argentina (Recruiting)
- Macquarie University ( Site 2700) — Macquarie University, New South Wales, Australia (Suspended)
- Rambam Health Care Campus ( Site 1600) — Haifa, Israel (Recruiting)
- Sheba Medical Center ( Site 1601) — Ramat Gan, Israel (Recruiting)
- Severance Hospital, Yonsei University Health System ( Site 2903) — Seoul, South Korea (Recruiting)
- Samsung Medical Center ( Site 2902) — Seoul, South Korea (Recruiting)
Study contacts
- Study coordinator: Toll Free Number
- Email: Trialsites@msd.com
- Phone: 1-888-577-8839
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.