A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-08032562 IN PARTICIPANTS WITH ADVANCED OR METASTATIC SOLID TUMORS
Summary
The purpose of this study is to learn about the safety and effects of the study medicine when given alone or together with other anti-cancer therapies. Anti-cancer therapy is a type of treatment to stop the growth of cancer. This study also aims to find the best amount of study medication. This study is seeking participants that have advanced or metastatic breast cancer (BC), or advanced or metastatic colorectal cancer (CRC). All participants in this study will take the study medication (PF-08032562) as pill by mouth. This will be repeated for 28-day cycles. Depending on which part of the study participants are enrolled into, they will receive the study medication PF-08032562 alone or in combination with other anti-cancer medications. The study medication (PF-08032562) will be taken by mouth (PO) in combination with other anti-cancer medications given in the study clinic by intramuscular (IM) injection into the muscle or intravenous (IV) infusion that is directly injected into the veins at different times (depending on the treatment) during the 28-day cycle. The study may also test different schedules.
Arms & interventions
- DrugPF-08032562
Taken by mouth (PO)
- DrugFulvestrant
Selective Estrogen Receptor Degrader (SERD)
- DrugCetuximab
Monoclonal antibody (EGFR inhibitor)
- DrugFluorouracil
Part of FOLFOX chemotherapy regimen cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
- DrugOxaliplatin
Part of FOLFOX chemotherapy regimen platinum based compound (alkylating agent)
- DrugLeucovorin
Part of FOLFOX chemotherapy regimen (folic acid analog)
- DrugBevacizumab
Monoclonal antibody (VEG-F inhibitor)
Outcome measures
Primary
Part 1 (Dose Escalation): Number of participants with Dose-Limiting Toxicities (DLT)
Any adverse events that are attributable to one, the other, or both study treatments, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes.
Time frame: Baseline up to 28 days
Part 1 (Dose Escalation): Number of participants with laboratory abnormalities
Number of participants with laboratory test abnormalities.
Time frame: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first
Part 1 (Dose Escalation): Incidence of Adverse Events (AEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.
Time frame: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first
Part 2 (Dose Expansion): Objective Response Rate (ORR)
ORR defined as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)
Secondary
Part 1 & Part 2: Maximum Observed Serum Concentration (Cmax)
Time frame: Baseline through end of Cycle 1 (each cycle is 28 days)
Part 1 & Part 2: Time to Reach Maximum Observed Serum Concentration (Tmax)
Time frame: Baseline through end of Cycle 1 (each cycle is 28 days)
Part 1: Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration (AUClast)
Time frame: Baseline through end of Cycle 1 (each cycle is 28 days)
Part 1: Effect of Food on Cmax
Time frame: Baseline through end of Cycle 1 (each cycle is 28 days)
Part 1: Effect of Food on Tmax
Time frame: Baseline through end of Cycle 1 (each cycle is 28 days)
Part 1: Effect of Food on AUClast
Time frame: Baseline through end of Cycle 1 (each cycle is 28 days)
Part 1: Percent change of immune cells within tumors based on immunohistochemistry assessment
Time frame: Baseline through end of Cycle 1 (each cycle is 28 days)
Part 2 (Dose Expansion): Number of participants with laboratory abnormalities
Time frame: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first
Part 2 (Dose Expansion): Incidence of Adverse Events (AEs)
Time frame: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first
Part 1 & Part 2: Objective Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)
Part 1 & Part 2: Disease Control Rate (DCR) as per RECIST v1.1
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)
Part 1 & Part 2: Clinical Benefit Rate (CBR) as per RECIST v1.1
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)
Part 1 & Part 2: Duration of Response (DOR) as per RECIST v1.1
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)
Part 1 & Part 2: Progression-Free Survival (PFS) as per RECIST v1.1
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)
Part 1 & Part 2: Time to Response (TTR) as per RECIST v1.1
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years)
Part 2: Overall Survival (OS)
Time frame: Up to approximately 2 years
Eligibility criteria
Study locations (9)
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010
START Midwest, LLC
Grand Rapids, Michigan, 49546
The University of Texas MD Anderson Cancer Center - Conroe
Conroe, Texas, 77384
The University of Texas - M.D. Anderson Cancer Center
Houston, Texas, 77030
The University of Texas, MD Anderson Cancer Center - West Houston
Houston, Texas, 77079
The University of Texas, MD Anderson Cancer Center - League City
League City, Texas, 77573
START San Antonio
San Antonio, Texas, 78229
The University of Texas, MD Anderson Cancer Center - Sugar Land
Sugar Land, Texas, 77478
START Mountain Region
West Valley City, Utah, 84119