A Study to Learn About the Study Medicine PF-07934040 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Genetic Mutation.
- Conditions
- Carcinoma, Non-Small-Cell LungCarcinoma, Pancreatic DuctalColorectal Neoplasms
- Interventions
- Combination Product: GemcitabineCombination Product: CetuximabCombination Product: FluorouracilCombination Product: PembrolizumabCombination Product: Nab-paclitaxelCombination Product: OxaliplatinCombination Product: pemetrexedCombination Product: LeucovorinCombination Product: CisplatinCombination Product: BevacizumabCombination Product: PaclitaxelCombination Product: Carboplatin
- Registration Number
- NCT06447662
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 330
- Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor.
ECOG PS 0 or 1
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Presence of at least 1 measurable lesion based on RECIST version 1.1 that has not been previously irradiated.
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Documentation of mutated KRAS gene
- PDAC, CRC, Other tumor types: Confirmed KRAS mutation, any variant
- NSCLC: Confirmed KRAS mutation, any variant except previously treated G12C. If driver mutation, must have failed precision medicine therapy [eg, inhibitors of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and others].
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Part 1 and Part 2a: Participant must have progressed on standard treatment(s) for which no additional, effective therapy is available.
- PDAC (2-3L): Participants must have received and radiologically progressed on prior lines of systemic therapy for metastatic pancreatic adenocarcinoma. If participants received prior neoadjuvant or adjuvant chemotherapy and progressed within 6 months of the last dose, then this should be considered as a prior line of systemic therapy.
- NSCLC (2-3L): Participants must have received prior lines of anti-cancer treatment and progressed on at least a platinum-containing chemotherapy regimen and checkpoint inhibitor therapy; for participants with EGFR, ALK, or other genomic tumor alterations, participants must have progressed on approved therapy for these alterations.
- CRC (2-3L): Participants must have had one or two prior systemic treatment regimens for mCRC. For either one or two prior treatments, these regimens must have included a fluoropyrimidine, oxaliplatin, or irinotecan; for one prior treatment, exposure to VEGF/VEGF receptor (VEGFR) inhibitor is optional;
- Other tumors: Participants, in the judgment of the investigator, must have progressed or become intolerant to all available standard therapies, or have refused such therapy.
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Part 2b:
- PDAC (1L) Cohort A2: Participants must not have received prior chemotherapy for metastatic disease. Participant could have received neoadjuvant therapy, adjuvant therapy, or adjuvant chemo-radiotherapy, as long as relapse did not occur within 6 months of completing these forms of adjuvant treatment. If so, the relapse within 6 months would be considered a line of therapy; the participant would be considered 2L, and not 1L.
- CRC (2-3L) Cohort B2: Participants must have had one or two prior systemic treatment regimens for mCRC. For either one or two prior treatments, these regimens must have included a fluoropyrimidine, irinotecan, oxaliplatin; for one prior treatment, exposure to a VEGF/VEGF receptor (VEGFR) inhibitor is optional.
- CRC (1L) Cohort B3: Participants must not have had prior chemotherapy for advanced or metastatic disease. Participant could have received adjuvant chemotherapy or adjuvant chemo-radiotherapy, as long as relapse did not occur within 6 months of complete of adjuvant therapy. If so, the relapse within 6 months would be considered a line of therapy; the participant would be considered 2L, and not 1L.
- NSCLC (1L) Cohort C2: Participants must have a TPS ≥50% and must not have received prior systemic treatment setting.
- NSCLC (1L) Cohort C3: Participants with any TPS and must not have received prior systemic treatment setting.
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Active or history of pneumonitis/ILD, pulmonary fibrosis requiring treatment with systemic steroid therapy, including evidence to suggest pneumonitis/ILD on baseline assessments including imaging.
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Diagnosis of immunodeficiency or an active autoimmune disease that require systemic treatment with chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy in the past 2 years.
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Sensory peripheral neuropathy ≥Grade 2
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Active or history of clinically significant gastrointestinal (GI) disease (including but not limited to inflammatory GI disease [eg, ulcerative colitis, Crohn's disease, inflammatory bowel disease], immune-mediated colitis, peptic ulcer disease, GI bleeding, chronic diarrhea) and other conditions that are unresolved and/or may increase the risk associated with study participation or study treatment administration.
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Active bleeding disorder, including GI bleeding, as evidenced by hematemesis, significant hemoptysis or melena in the past 6 months.
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Major surgery or completion of radiation therapy ≤4 weeks prior to enrollment/randomization or radiation therapy that included >30% of the bone marrow.
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Known sensitivity or contraindication to any component of study intervention (PF 07934040, gemcitabine, nab-paclitaxel, cetuximab, bevacizumab, FOLFOX, 5-FU, pembrolizumab, cisplatin, carboplatin, pemetrexed, SHP2 inhibitor(s), cyclin-dependent kinase (CDK) inhibitor(s), antibody drug conjugates (ADCs) or EGFR inhibitor(s)).
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Hematologic abnormalities.
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Renal impairment.
- Hepatic abnormalities.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2a Cohort B1 PF-07934040 Monotherapy dose expansion in 2-3L CRC. PF-07934040 at prescribed dose and frequency in 28-day cycles Part 1 PF-07934040 PF-07934040 Monotherapy Dose Escalation PF-07934040 monotherapy at prescribed dose and frequency in 28-day cycles Part 2a Cohort A1 PF-07934040 Monotherapy dose expansion in 2-3L PDAC. PF-07934040 at prescribed dose and frequency in 28-day cycles Part 2b Cohort B3 Bevacizumab Combination (PF-07934040 + FOLFOX + Bevacizumab) dose escalation/expansion in 1L CRC Prescribed dose and frequency in 28-day cycles Part 2a Cohort C1 PF-07934040 Monotherapy dose expansion in 2-3L NSCLC. PF-07934040 at prescribed dose and frequency in 28-day cycles Part 2b Cohort A2 Gemcitabine Combination (PF-07934040 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles Part 2b Cohort A2 Nab-paclitaxel Combination (PF-07934040 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles Part 2b Cohort B2 Cetuximab Combination (PF-07934040 + Cetuximab) dose escalation/expansion in 2-3L CRC Prescribed dose and frequency in 28-day cycles Part 2b Cohort B3 Fluorouracil Combination (PF-07934040 + FOLFOX + Bevacizumab) dose escalation/expansion in 1L CRC Prescribed dose and frequency in 28-day cycles Part 2b Cohort B3 Oxaliplatin Combination (PF-07934040 + FOLFOX + Bevacizumab) dose escalation/expansion in 1L CRC Prescribed dose and frequency in 28-day cycles Part 2b Cohort B3 Leucovorin Combination (PF-07934040 + FOLFOX + Bevacizumab) dose escalation/expansion in 1L CRC Prescribed dose and frequency in 28-day cycles Part 2b Cohort C3 Carboplatin Combination (PF-07934040 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles Part 2b Cohort C2 PF-07934040 Combination (PF-07934040 + Pembro) dose escalation/expansion in 1L NSCLC (TPS ≥ 50%) Prescribed dose and frequency in 21-day cycles Part 2b Cohort C2 Pembrolizumab Combination (PF-07934040 + Pembro) dose escalation/expansion in 1L NSCLC (TPS ≥ 50%) Prescribed dose and frequency in 21-day cycles Part 2b Cohort C3 PF-07934040 Combination (PF-07934040 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles Part 2b Cohort C3 Pembrolizumab Combination (PF-07934040 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles Part 2b Cohort C3 pemetrexed Combination (PF-07934040 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles Part 2b Cohort C3 Cisplatin Combination (PF-07934040 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles Part 2b Cohort C3 Paclitaxel Combination (PF-07934040 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles Part 2b Cohort A2 PF-07934040 Combination (PF-07934040 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles Part 2b Cohort B2 PF-07934040 Combination (PF-07934040 + Cetuximab) dose escalation/expansion in 2-3L CRC Prescribed dose and frequency in 28-day cycles Part 2b Cohort B3 PF-07934040 Combination (PF-07934040 + FOLFOX + Bevacizumab) dose escalation/expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
- Primary Outcome Measures
Name Time Method Part 1 & 2: Incidence of Adverse Events (AEs) Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first) 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.
PART 1 & 2: Number of participants with laboratory abnormalities From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first 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).
Part 1: Number of participants with Dose-limiting toxicities (DLT) Baseline up to 28 days 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
Part 2: Objective Response - Number of Participants With Objective Response (alone or in combination) Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years' 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.
- Secondary Outcome Measures
Name Time Method Part 1& 2: Time to Reach Maximum Observed Serum Concentration (Tmax) Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days) Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.
Part 1: Effect of Food on AUClast Baseline through end of Cycle 1 (All cycles are 28 days) Evaluate the effect of food on AUClast of PF-07934040 as monotherapy.
Part 1: Effect of Food on Tmax Baseline through end of Cycle 1 (All cycles are 28 days) Evaluate the effect of food on Tmax of PF-07934040 as monotherapy.
Part 1 & 2: Changes in pERK levels Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days) Evaluates the intended mechanism of action (MoA) modulation of KRAS inhibition and target engagement effect of PF-07934040 in peripheral blood of participants with advanced solid tumor malignancies.
Part 1: Objective Response - Number of Participants With Objective Response Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years 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) assessed by the Investigator including overall response rate (ORR), progression free survival (PFS), and overall survival (OS).
Part 1: Effect of Food on Cmax Baseline through end of Cycle 1 (All cycles are 28 days) Evaluate the effect of food on Cmax of PF-07934040 as monotherapy.
Part 1 & 2: Maximum Observed Serum Concentration (Cmax) baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days) Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.
Part 1 & 2: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days) Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.
Trial Locations
- Locations (23)
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
🇺🇸Aurora, Colorado, United States
Highlands Oncology Group, PA
🇺🇸Rogers, Arkansas, United States
City of Hope Investigational Drug Service (IDS)
🇺🇸Duarte, California, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)
🇺🇸Aurora, Colorado, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Siteman Cancer Center - North County
🇺🇸Florissant, Missouri, United States
Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - St Peters
🇺🇸Saint Peters, Missouri, United States
West Chester Hospital
🇺🇸West Chester, Ohio, United States
Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
🇺🇸Duarte, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Pan American Center for Oncology Trials, LLC
🇵🇷Rio Piedras, Puerto Rico