A Phase 1 Open-Label Study of PF-07934040 as a Single Agent and in Combination With Other Targeted Agents in Participants With Advanced Solid Tumors Harboring Mutations in the KRAS Gene
Summary
The purpose of this study is to learn about the safety and effects of the study medicine alone or when given together with other anti-cancer therapies. This study also aims to find the best dose. This study is seeking participants who have solid tumors (a mass of abnormal cells that forms a lump or growth in the body) that: * are advanced (cancer that doesn't disappear or stay away with treatment) and * have a KRAS gene mutation (a change in the DNA of the KRAS gene that can cause cells to grow in very high numbers). This includes (but limited to) the following cancer types: Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body. Colorectal Cancer (CRC): This is a disease where cells in the colon (a part of large intestine) or rectum grow out of control. Pancreatic ductal adenocarcinoma (PDAC): This is a cancer that starts in the ducts of the pancreas but can spread quickly to other parts of the body. Pancreas is a long, flat gland that lies in the abdomen behind the stomach. Pancreas creates enzymes that help with digestion. It also makes hormones that can help control your blood sugar levels. All participants in this study will take the study medication (PF-07934040) as pill by mouth twice a day repeating for 21-day or 28-day cycles. Depending on which part of the study participants are enrolled into they will receive the study medication (PF-07934040 alone or in combination with other anti-cancer medications). These anti-cancer medications will be given in the study clinic by intravenous (IV) that is directly injected into the veins at various times (depending on the treatment) during the 21-day or 28-day cycle. Participants can continue to take the study medication (PF-07934040) and the combination anti-cancer therapy until their cancer is no longer responding. The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective. Participants will be involved in this study for up to 4 years. During this time, they will come into the clinic between 1 to 4 times in each 21-day or 28-day cycle. After they have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing.
Arms & interventions
- DrugPF-07934040
panKRAS inhibitor
- Combination ProductGemcitabine
Chemotherapy (antimetabolite)
- Combination ProductNab-paclitaxel
Taxane-type Chemotherapy
- Combination ProductCetuximab
Monoclonal Antibody (EGFR Inhibitor)
- Combination ProductFluorouracil
Part of FOLFOX chemotherapy regimen cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
- Combination ProductOxaliplatin
Part of FOLFOX Chemotherapy Regimen platinum based compound (alkylating agent)
- Combination ProductLeucovorin
Part of FOLFOX chemotherapy regimen Folic Acid Analog
- Combination ProductBevacizumab
VEG-F inhibitor
- Combination ProductPembrolizumab
immune checkpoint inhibitor (PD-1 inhibitor)
- Combination Productpemetrexed
Can be used in Platinum-based Chemotherapy regimen Antimetabolite
- Combination ProductCisplatin
Can be used as part of Platinum-based chemotherapy regimen Platinum-based antineoplastic (alkylating agent)
- Combination ProductPaclitaxel
Can be used in Platinum-based chemotherapy regimen Taxane
- Combination ProductCarboplatin
Can be used as part of a platinum-based chemotherapy regimen platinum containing compound (alkylating agent)
- Combination ProductSasanlimab
immune checkpoint inhibitor (PD-1 inhibitor)
Outcome measures
Primary
Part 1 & 2: 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. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.
Time frame: Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first)
PART 1 & 2: Number of participants with laboratory abnormalities
Number of participants with laboratory test abnormalities. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).
Time frame: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first
Part 1: Number of participants with Dose-limiting toxicities (DLT)
Any of the prespecified AEs 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 2: Objective Response - Number of Participants With Objective Response (alone or in combination)
Percentage of participants with objective response-based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for overall response rate (ORR), progression free survival (PFS), and overall survivor (OS) assessed by the Investigator.
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 & 2: Maximum Observed Serum Concentration (Cmax)
Time frame: baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)
Part 1& 2: Time to Reach Maximum Observed Serum Concentration (Tmax)
Time frame: Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)
Part 1 & 2: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time frame: Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)
Part 1 & 2: Changes in pERK levels
Time frame: Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)
Part 1: Objective Response - Number of Participants With Objective Response
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: Effect of Food on Cmax
Time frame: Baseline through end of Cycle 1 (All cycles are 28 days)
Part 1: Effect of Food on Tmax
Time frame: Baseline through end of Cycle 1 (All cycles are 28 days)
Part 1: Effect of Food on AUClast
Time frame: Baseline through end of Cycle 1 (All cycles are 28 days)
Eligibility criteria
Study locations (26)
Highlands Oncology Group, PA
Fayetteville, Arkansas, 72703
Highlands Oncology Group, PA
Rogers, Arkansas, 72758
Highlands Oncology Group
Springdale, Arkansas, 72762
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010
City of Hope Investigational Drug Service (IDS)
Duarte, California, 91010
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
Aurora, Colorado, 80045
University of Colorado Hospital - Anschutz Outpatient Pavilion
Aurora, Colorado, 80045
University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)
Aurora, Colorado, 80045
University of Colorado Hospital
Aurora, Colorado, 80045
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
START Midwest
Grand Rapids, Michigan, 49546
Siteman Cancer Center - St Peters
City of Saint Peters, Missouri, 63376
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141
Siteman Cancer Center - North County
Florissant, Missouri, 63031
Siteman Cancer Center
St Louis, Missouri, 63108
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center - South County
St Louis, Missouri, 63129
Duke University Medical Center, lnvestigational Chemotherapy Service
Durham, North Carolina, 27710
Duke University Medical Center
Durham, North Carolina, 27710
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
West Chester Hospital
West Chester, Ohio, 45069
Rhode Island Hospital
Providence, Rhode Island, 02903
Miriam Hospital
Providence, Rhode Island, 02906
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030