A Study to Evaluate the Safety, Tolerability, and Efficacy of Pumitamig Alone or in Combination With Other Agents in Participants With Advanced Renal Cell Carcinoma (RCC) (ROSETTA RCC-208)
The purpose of this study is to evaluate the safety, tolerability, and efficacy of Pumitamig alone or in combination with other agents in participants with advanced Renal Cell Carcinoma (RCC)
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
iv) For Parts 2D and 2E: Prior treatment with a HIF-2α inhibitor or other agent that targets the HIF-2α pathway is not allowed.
\- 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, left ventricular ejection fraction (LVEF) \<50% (for Part 2D and 2E) or congenital long QT syndrome.
* Participants must not have a urine protein ≥ 2+ on dipstick or urinalysis at baseline and confirmed proteinuria ≥ 1 g/24 hours or urine protein-creatinine ratio (UPCR) \> 1000 mg/g.
* 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.
* For Part 2D and 2E: Receiving ongoing concomitant treatment with sensitive substrates of CYP3A4, CYP2C8, CYP2C9, or CYP2C19 with narrow therapeutic indices within 5 half-lives of the concomitant treatment or up to 28 days, whichever is shorter, prior to randomization.
* For Part 2D and 2E: Receiving ongoing concomitant treatment with moderate or strong CYP3A4 inducers, or moderate or strong CYP3A4 inhibitors within 5 half-lives of the concomitant treatment, or up to 28 days, whichever is shorter, prior to randomization.
* For Part 2D and 2E: Has hypoxia defined by a pulse oximeter reading \< 92% at rest or requires intermittent or chronic supplemental oxygen.
* For Part 2D and 2E: Exercise-induced desaturation on a 6-minute walk test, defined as a blood oxygen saturation by pulse oximetry ≤ 88%.
* For Part 2D and 2E: Presence of significant pulmonary disease/condition (eg, chronic obstructive pulmonary disease, pleural effusion, etc) that, in the opinion of the Investigator, could put participant at increased risk from study intervention or impact interpretation of safety data.
* Other protocol-defined Inclusion/Exclusion criteria apply.
Primary outcome measure(s)
Number of participants with adverse events (AEs) — Up to approximately 2 years from end of treatment Phase 1
Number of participants with serious adverse events (SAEs) (as per Common Terminology Criteria for Adverse Events v5 (CTCAE v5)) — Up to approximately 2 years from end of treatment Phase 1
Number of participants with AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria — Up to day 21 from first dose Phase 1
Number of participants with AEs leading to discontinuation — Up to approximately 2 years from end of treatment Phase 1
Number of participants with AEs leading to death — Up to approximately 2 years from end of treatment Phase 1
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 — Up to approximately 2 years from end of treatment Phase 2
Trial sites (96)
Facility
City
Region
Status
Local Institution - 0178
Palo Alto
California
Not Yet Recruiting
Local Institution - 0117
New Haven
Connecticut
Not Yet Recruiting
Sibley Memorial Hospital
Washington D.C.
District of Columbia
Recruiting
Local Institution - 0177
Miami
Florida
Not Yet Recruiting
Local Institution - 0126
Orlando
Florida
Not Yet Recruiting
Local Institution - 0175
Atlanta
Georgia
Not Yet Recruiting
Local Institution - 0170
Fort Wayne
Indiana
Not Yet Recruiting
University Of Iowa Hospitals And Clinics
Iowa City
Iowa
Recruiting
Johns Hopkins Hospital
Baltimore
Maryland
Recruiting
Local Institution - 0176
Big Rapids
Michigan
Not Yet Recruiting
Washington University School of Medicine
St Louis
Missouri
Recruiting
Memorial Sloan Kettering Cancer Center
New York
New York
Recruiting
Local Institution - 0135
Cincinnati
Ohio
Not Yet Recruiting
Cleveland Clinic
Cleveland
Ohio
Recruiting
MUSC Hollings Cancer Center
Charleston
South Carolina
Recruiting
Carolina Urologic Research Center, LLC
Myrtle Beach
South Carolina
Recruiting
Local Institution - 0158
Salt Lake City
Utah
Withdrawn
Local Institution - 0095
Seattle
Washington
Not Yet Recruiting
Asociación de Beneficencia Hospital Sirio Libanés
Ciudad Autonoma de Buenos Aires
Buenos Aires
Recruiting
Instituto Medico Especializado Alexander Fleming
Buenos Aires
Argentina
Recruiting
Local Institution - 0156
Buenos Aires
Argentina
Not Yet Recruiting
Macquarie University
North Ryde
New South Wales
Recruiting
GenesisCare St Leonards
St Leonards
New South Wales
Recruiting
Mater Misericordiae Limited
Brisbane
Queensland
Recruiting
Local Institution - 0011
Herston
Queensland
Not Yet Recruiting
Local Institution - 0004
Heidelberg
Victoria
Not Yet Recruiting
Local Institution - 0003
Malvern
Australia
Not Yet Recruiting
Local Institution - 0007
Calgary
Alberta
Not Yet Recruiting
Local Institution - 0189
Edmonton
Alberta
Not Yet Recruiting
Local Institution - 0109
Montreal
Quebec
Withdrawn
Local Institution - 0009
Montreal
Quebec
Not Yet Recruiting
Local Institution - 0006
Québec
Quebec
Not Yet Recruiting
Local Institution - 0105
Santiago
Santiago Metropolitan
Not Yet Recruiting
Bradfordhill
Santiago
Santiago Metropolitan
Recruiting
Local Institution - 0163
Santiago
Chile
Not Yet Recruiting
Local Institution - 0143
Beijing
Beijing Municipality
Not Yet Recruiting
Local Institution - 0157
Beijing
Beijing Municipality
Not Yet Recruiting
Local Institution - 0182
Guangzhou
Guangdong
Not Yet Recruiting
Local Institution - 0145
Tianjin
Hebei
Not Yet Recruiting
Local Institution - 0187
Harbin
Heilongjiang
Not Yet Recruiting
+ 56 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.