A Study to Evaluate the Safety, Tolerability, and Efficacy of Pumitamig Alone or in Combination With Ipilimumab or Cabozantinib in Participants With Advanced Renal Cell Carcinoma (RCC) (ROSETTA RCC-208)

Official title

ROSETTA RCC-208: A Phase 1/2 Open-label, Multi-center, Randomized Study of Pumitamig Alone or in Combination With Ipilimumab or Cabozantinib in Participants With Advanced Renal Cell Carcinoma (RCC)

Overview

The purpose of this study is to evaluate the safety, tolerability, and efficacy of Pumitamig alone or in combination with Ipilimumab or Cabozantinib in participants with advanced Renal Cell Carcinoma (RCC)

Interventions

• Drug Pumitamig
  Specified dose on specified days
• Drug Ipilimumab
  Specified dose on specified days
• Drug Cabozantinib
  Specified dose on specified days

Primary outcome measures

• Number of participants with adverse events (AEs) [Time frame: Up to approximately 2 years from end of treatment]
• Number of participants with serious adverse events (SAEs) (as per Common Terminology Criteria for Adverse Events v5 (CTCAE v5)) [Time frame: Up to approximately 2 years from end of treatment]
• Number of participants with AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria [Time frame: Up to day 21 from first dose]
• Number of participants with AEs leading to discontinuation [Time frame: Up to approximately 2 years from end of treatment]
• Number of participants with AEs leading to death [Time frame: Up to approximately 2 years from end of treatment]
• Objective response rate (ORR) (confirmed complete response (CR) or partial response (PR)) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment [Time frame: Up to approximately 2 years from end of treatment]

Secondary outcome measures (7)

• Number of participants with AEs [Time frame: Up to approximately 2 years from end of treatment]
• Number of participants with SAEs (as per CTCAE v5) [Time frame: Up to approximately 2 years from end of treatment]
• Number of participants with treatment-related adverse events (TRAEs) [Time frame: Up to approximately 2 years from end of treatment]
• Number of participants with AEs leading to discontinuation [Time frame: Up to approximately 2 years from end of treatment]
• Number of participants with AEs leading to death [Time frame: Up to approximately 2 years from end of treatment]
• Progression-free survival (PFS) by RECIST v1.1 per investigator assessment [Time frame: Up to 4 years from randomization]
• Duration of response (DOR) (PR or CR) by RECIST v1.1 per investigator assessment [Time frame: Up to approximately 2 years from end of treatment]

Eligibility criteria

Inclusion criteria

• Participants must have a histologically confirmed diagnosis of locally advanced, unresectable (not amenable to curative surgery or radiation therapy) or metastatic Renal Cell Carcinoma (RCC).
• Participants must have clear cell RCC (ccRCC) or non-clear cell RCC (nccRCC) may be enrolled in Part 1. Note: Part 2 may only enroll participants with ccRCC.
• Participants may have favorable, intermediate or poor risk disease categories.
• Participants must not have received prior systemic therapy for metastatic RCC, with the following exceptions:

i) One prior adjuvant or neoadjuvant therapy for completely resectable RCC is allowed if such therapy did not include an agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy.

ii) For Part 1A participants: Prior systemic therapy in the metastatic setting is allowed if the participant has not received any therapy targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) (e.g., ipilimumab).

iii) For Part 1B participants: Prior systemic therapy in the metastatic setting is allowed if the participant has not received prior treatment with cabozantinib.

\- Participants must have measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Exclusion criteria

• Participants must not have any untreated known CNS metastases.
• Participants must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of Cycle 1 Day1 (C1D1).
• Participants must not have a history of interstitial lung disease or pneumonitis.
• Participants must not have an uncontrolled pleural or pericardial effusion requiring recurrent therapeutic drainage procedures.
• Participants must not have significant cardiovascular disease, such as myocardial infarction, unstable angina, arterial thrombosis, cerebrovascular accident within 6 months prior to C1D1, uncontrolled hypertension (≥ 150 systolic, ≥ 90 diastolic mm Hg) despite optimal medical management, or congenital long QT syndrome.
• Participants must not have a urine protein ≥ 2+ and 24 hour urine protein ≥ 1 g at baseline.
• Participants must not have evidence of major coagulation disorders.
• Participants must not have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism within 6 months prior to C1D1.
• Participants must not have a history of abdominal fistula or gastrointestinal (GI) perforation within 6 months.
• Participants must not have had a major surgery or trauma within 28 days prior to C1D1.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 18 centers

• Local Institution - 0178 — Palo Alto
• Local Institution - 0117 — New Haven
• Sibley Memorial Hospital — Washington D.C.
• Local Institution - 0177 — Miami
• Local Institution - 0126 — Orlando
• Local Institution - 0175 — Atlanta
• Local Institution - 0170 — Fort Wayne
• Local Institution - 0124 — Iowa City
• … and 10 more centers

United Kingdom · 8 centers

Center list to be confirmed — check the primary protocol.

China · 7 centers

• Local Institution - 0143 — Beijing
• Local Institution - 0157 — Beijing
• Local Institution - 0182 — Guangzhou
• Local Institution - 0183 — Changsha Shi
• Local Institution - 0184 — Nanjing
• Local Institution - 0188 — Shanghai Shi
• Local Institution - 0144 — Beijing

Japan · 6 centers

• Local Institution - 0180 — Kobe
• Local Institution - 0179 — Shiwa-gun Yahaba-cho
• The Cancer Institute Hospital of JFCR — Koto-ku
• Local Institution - 0078 — Toyoma
• Kyushu University Hospital — Fukuoka
• Local Institution - 0181 — Niigata

Mexico · 6 centers

• Local Institution - 0046 — Monterrey
• Local Institution - 0048 — Oaxaca City
• Local Institution - 0122 — Puebla City
• Local Institution - 0049 — Tlalpan
• Local Institution - 0108 — Tlalpan
• Local Institution - 0118 — Tlalpan

Australia · 5 centers

• Macquarie University — North Ryde
• GenesisCare St Leonards — St Leonards
• Local Institution - 0011 — Herston
• Local Institution - 0074 — South Brisbane
• Local Institution - 0003 — Malvern

Germany · 4 centers

• Local Institution - 0025 — Jena
• Local Institution - 0026 — Hamburg
• Local Institution - 0014 — Herne
• Local Institution - 0027 — München

Romania · 4 centers

• Local Institution - 0103 — Cluj-Napoca
• Local Institution - 0161 — Craiova
• Local Institution - 0100 — Iași
• Local Institution - 0101 — Sibiu

Canada · 3 centers

• Local Institution - 0007 — Calgary
• Local Institution - 0109 — Montreal
• Local Institution - 0009 — Montreal

Chile · 3 centers

• Local Institution - 0105 — Santiago
• Bradfordhill — Santiago
• Local Institution - 0163 — Santiago

Czechia · 3 centers

• Local Institution - 0147 — Prague
• Local Institution - 0149 — Brno
• Local Institution - 0150 — Hradec Králové

Finland · 3 centers

• Local Institution - 0044 — Helsinki
• Local Institution - 0029 — Turku
• Local Institution - 0060 — Vantaa

France · 3 centers

• Local Institution - 0083 — Lille
• Local Institution - 0080 — Boredeaux
• Local Institution - 0028 — Villejuif

Italy · 3 centers

• Local Institution - 0139 — Verona
• Local Institution - 0073 — Milan
• Local Institution - 0087 — Napoli Campania

South Korea · 3 centers

• Local Institution - 0112 — Seoul
• Local Institution - 0017 — Seoul
• Local Institution - 0167 — Seoul

Spain · 3 centers

• Local Institution - 0013 — Madrid
• Local Institution - 0091 — Madrid
• Local Institution - 0043 — Seville

Switzerland · 3 centers

Center list to be confirmed — check the primary protocol.

Argentina · 2 centers

• Instituto Medico Especializado Alexander Fleming — Buenos Aires
• Local Institution - 0156 — Buenos Aires

Ireland · 2 centers

• Local Institution - 0059 — Dublin
• Local Institution - 0062 — Dublin

Brazil · 1 center

• Hospital Sirio Libanes — Brasília

Colombia · 1 center

• Local Institution - 0052 — Cali

Identifiers

NCT: NCT07293351 · CA266-0008 · 2025-523637-26 · U1111-1327-6332

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗