AN INTERVENTIONAL PHASE 1B/2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF-08634404 MONOTHERAPY AND IN COMBINATION WITH OTHER ANTICANCER AGENTS IN ADULT PARTICIPANTS WITH LOCALLY ADVANCED OR METASTATIC RENAL CELL CARCINOMA
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Pfizer
- Enrollment
- 224
- Locations
- 187
- Primary Endpoint
- Confirmed objective response rate (ORR) using RECIST v1.1 as assessed by investigator
Study Overview
Brief Summary
This study is testing a new medicine called PF-08634404 and how it works in adults with advanced Renal Cell Carcinoma (RCC)- a type of kidney cancer that is either locally advanced (spread to nearby tissues) or metastatic (spread to other parts of the body). The study will look at the safety of the study medicine, when given alone or with other anticancer medicines, and how this type of cancer responds to them.
To join the study, participants must be adults; with locally advanced or metastatic RCC; who have not received treatment for their advanced kidney cancer.
Participants will receive study medicine either alone or with other anticancer medicines. The medicine will be given through intravenous (IV) infusions, which means it will be injected directly into a vein. All treatments will take place at clinical study sites, where trained medical staff will take care of participants during and after each visit.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18 years of age or older at screening
- •Locally advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC with diagnosis confirmed by histology/cytology
- •At least one measurable (as defined by the investigator) and untreated lesion
- •Adequate hematologic, hepatic, cardiac and renal function
- •No prior systemic therapy for RCC (immunotherapy after surgery is allowed if received >12 months prior)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •All International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) based risk categories
Exclusion Criteria
- •Participants may be excluded if they meet any of the following:
- •Known active brain lesions including leptomeningeal metastasis, brainstem, meningeal or spinal cord metastases or compression.
- •Clinically significant risk of haemorrhage or fistula
- •History of another malignancy within 3 years
- •History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- •active autoimmune diseases requiring systemic treatment within the past 2 years
- •uncontrolled cardiac and other comorbidities within 6 months prior to the first dose
- •Major surgery or severe trauma within 4 weeks before the first dose, or planned major surgery during the study
- •History of severe bleeding tendency or coagulation dysfunction
- •History of oesophageal varices, severe ulcers, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess or acute gastrointestinal bleeding within 6 months prior to the first dose
- •Acute, chronic or symptomatic infections
- •Participants with history of immunodeficiency
Arms & Interventions
Cohort A
Participants will receive PF-08634404 IV.
Intervention: PF-08634404 (Drug)
Cohort B
Participants will receive PF-08634404 in combination with ipilimumab.
Intervention: PF-08634404 (Drug)
Cohort C
Participants will receive PF-08634404 IV in combination with axitinib.
Intervention: PF-08634404 (Drug)
Cohort D
Participants will receive PF-08634404 in combination with Casdatifan.
Intervention: PF-08634404 (Drug)
Cohort D
Participants will receive PF-08634404 in combination with Casdatifan.
Intervention: Casdatifan (Drug)
Cohort B
Participants will receive PF-08634404 in combination with ipilimumab.
Intervention: Ipilimumab (Drug)
Cohort C
Participants will receive PF-08634404 IV in combination with axitinib.
Intervention: Axitinib (Drug)
Outcomes
Primary Outcomes
Confirmed objective response rate (ORR) using RECIST v1.1 as assessed by investigator
Time Frame: Up to approximately 3 years
ORR is defined as the proportion of participants in the analysis population having a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v1.1 as assessed by investigator.
Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Through 90 days after the last study intervention (Up to approximately 3 years)
AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
Number of participants with dose limiting toxicity (DLT)
Time Frame: Though end of DLT evaluation period (Up to approximately 3 years)
The number of participants who experienced DLTs during the DLT evaluation period in Cohort B (combination 1) and Cohort C (combination 2).
Secondary Outcomes
- Duration of Response (DOR) per RECIST v1.1 by investigator(Up to approximately 3 years)
- Progression Free Survival (PFS) per RECIST v1.1 by investigator(Up to approximately 3 years)
- Overall Survival (OS)(Up to approximately 3 years)
- Number of Participants With Clinical Laboratory Abnormalities(Time from the date of first dose of study intervention through 30-37 days after last dose of study intervention (approximately 3 years))
- Pharmacokinetics (PK): Serum concentration of PF-08634404(Up to 37 days after the last dose of treatment)
- Incidence of Anti-Drug Antibody (ADA) against PF-08634404(Up to 37 days after the last dose of treatment)