Table 3.
Trial in progress for combination immune checkpoint inhibitor and anti-angiogenic therapies in advanced-stage clear-cell renal cell carcinoma, as obtained from clinicaltrials.gov.
| Trial | Phase | Population | Treatment | Estimated Enrollment | Primary Endpoints | Estimated Primary Study Completion |
|---|---|---|---|---|---|---|
| COSMIC 313 NCT03937219 |
III | Previously untreated, unresectable/metastatic renal cell carcinoma with a clear-cell component IMDC intermediate or poor risk |
Arm 1: Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab Arm 2: Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab |
840 | PFS | November 2021 |
| CONTACT-03 NCT04338269 |
III | Advanced, untreated RCC ccRCC and nccRCC cohorts |
Arm 1: Atezolizumab 1200 mg IV Q3W + cabozantinib 60 mg PO daily Arm 2: Cabozantinib 60 mg PO daily |
500 | PFS, OS | December 2022 |
| PEDIGREE NCT03793166 |
III | Unresectable/metastatic RCC with clear-cell component, including patients with sarcomatoid features IMDC intermediate and poor risk |
Induction ipilimumab + nivolumab. In patients with non-CR/non-PD: Arm 1: maintenance nivolumab alone Arm 2: maintenance nivolumab plus cabozantinib |
1046 | OS | September 2022 |
| TiNivo-2 NCT04987203 |
III | Advanced RCC with a clear component, progressed during or following at least 6 weeks of ICI treatment in the first- or second- line setting | Arm 1: Nivolumab IV Q4W plus tivozanib 1.34 mg PO daily, 3 weeks on treatment followed by 1 week off treatment Arm 2: Tivozanib 1.34 mg PO daily, 3 weeks on treatment followed by 1 week off treatment |
326 | PFS | July 2024 |
| TIDE-A NCT04698213 |
II | Metastatic RCC with predominately clear-cell subtype with primary tumor resected | Axitinib 5 mg PO BD + avelumab 10 mg/kg IV Q2W | 75 | ORR | September 2023 |
| NCT03172754 | I/II | Untreated, advanced RCC with predominately clear-cell subtype | Axitinib + nivolumab | 98 | TRAE, ORR |
April 2023 |
| NCT03149822 | I/II | Advanced or metastatic RCC | Cabozantinib + pembrolizumab | 45 | ORR | December 2020 |
| MK-3475-03A NCT04626479 |
I/II | Untreated, locally advanced or metastatic clear-cell RCC | Pembrolizumab + favezelimab Pembrolizumab + belzutifan Pembrolizumab + MK-4830 Pembrolizumab + lenvatinib Lenvatinib + belzutifan Pembrolizumab + quavonlimab |
390 | TRAE | June 2025 |
| MK-3475-03B NCT04626518 |
I/II | Locally advanced or metastatic ccRCC | Pembrolizumab + favezelimab Pembrolizumab + belzutifan Pembrolizumab + MK-4830 Pembrolizumab + lenvatinib Lenvatinib + belzutifan Pembrolizumab + quavonlimab |
370 | TRAE | May 2025 |
| NCT03634540 | II | Locally advanced or metastatic ccRCC Cohort 1: previously treated Cohort 2: immunotherapy-naïve |
Belzutifan 120 mg PO daily + cabozantinib 60 mg PO daily | 118 | ORR | August 2025 |
Abbreviations: RCC = renal cell carcinoma; IMDC = international metastatic RCC database consortium; PFS = progression-free survival; IV = intravenous; PO = per oral; OS = overall survival; non-CR = non-complete response; non-PD = non-progressive disease; ICI = immune checkpoint inhibitor; ccRCC = clear-cell RCC; nccRCC = non-clear-cell RCC; Q2W = every 2 weeks; Q3W = every 3 weeks; Q4W = every 4 weeks; ORR = overall response rate; TRAE = treatment-related adverse events.