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.
NCT ID: NCT06447662
Last Updated: 2025-12-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
330 participants
INTERVENTIONAL
2024-06-27
2028-09-09
Brief Summary
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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
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Part 1
PF-07934040 Monotherapy Dose Escalation PF-07934040 monotherapy at prescribed dose and frequency in 28-day cycles
PF-07934040
panKRAS inhibitor
Part 2a Cohort A1
Monotherapy dose expansion in 2-3L PDAC. PF-07934040 at prescribed dose and frequency in 28-day cycles
PF-07934040
panKRAS inhibitor
Part 2a Cohort B1
Monotherapy dose expansion in 2-3L CRC. PF-07934040 at prescribed dose and frequency in 28-day cycles
PF-07934040
panKRAS inhibitor
Part 2a Cohort C1
Monotherapy dose expansion in 2-3L NSCLC. PF-07934040 at prescribed dose and frequency in 28-day cycles
PF-07934040
panKRAS inhibitor
Part 2b Cohort A2
Combination (PF-07934040 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC.
Prescribed dose and frequency in 28-day cycles
PF-07934040
panKRAS inhibitor
Gemcitabine
Chemotherapy (antimetabolite)
Nab-paclitaxel
Taxane-type Chemotherapy
Part 2b Cohort B2
Combination (PF-07934040 + Cetuximab) dose escalation/expansion in 2-3L CRC
Prescribed dose and frequency in 28-day cycles
PF-07934040
panKRAS inhibitor
Cetuximab
Monoclonal Antibody (EGFR Inhibitor)
Part 2b Cohort B3
Combination (PF-07934040 + FOLFOX + Bevacizumab) dose escalation/expansion in 1L CRC
Prescribed dose and frequency in 28-day cycles
PF-07934040
panKRAS inhibitor
Fluorouracil
Part of FOLFOX chemotherapy regimen
cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
Oxaliplatin
Part of FOLFOX Chemotherapy Regimen
platinum based compound (alkylating agent)
Leucovorin
Part of FOLFOX chemotherapy regimen
Folic Acid Analog
Bevacizumab
VEG-F inhibitor
Part 2b Cohort C2
Combination (PF-07934040 + Pembro) dose escalation/expansion in 1L NSCLC (TPS ≥ 50%)
Prescribed dose and frequency in 21-day cycles
PF-07934040
panKRAS inhibitor
Pembrolizumab
immune checkpoint inhibitor (PD-1 inhibitor)
Part 2b Cohort C3
Combination (PF-07934040 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS)
Prescribed dose and frequency in 21-day cycles
PF-07934040
panKRAS inhibitor
Pembrolizumab
immune checkpoint inhibitor (PD-1 inhibitor)
pemetrexed
Can be used in Platinum-based Chemotherapy regimen
Antimetabolite
Cisplatin
Can be used as part of Platinum-based chemotherapy regimen
Platinum-based antineoplastic (alkylating agent)
Paclitaxel
Can be used in Platinum-based chemotherapy regimen
Taxane
Carboplatin
Can be used as part of a platinum-based chemotherapy regimen
platinum containing compound (alkylating agent)
Interventions
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PF-07934040
panKRAS inhibitor
Gemcitabine
Chemotherapy (antimetabolite)
Nab-paclitaxel
Taxane-type Chemotherapy
Cetuximab
Monoclonal Antibody (EGFR Inhibitor)
Fluorouracil
Part of FOLFOX chemotherapy regimen
cytotoxic chemotherapy (antimetabolite and pyrimidine analog)
Oxaliplatin
Part of FOLFOX Chemotherapy Regimen
platinum based compound (alkylating agent)
Leucovorin
Part of FOLFOX chemotherapy regimen
Folic Acid Analog
Bevacizumab
VEG-F inhibitor
Pembrolizumab
immune checkpoint inhibitor (PD-1 inhibitor)
pemetrexed
Can be used in Platinum-based Chemotherapy regimen
Antimetabolite
Cisplatin
Can be used as part of Platinum-based chemotherapy regimen
Platinum-based antineoplastic (alkylating agent)
Paclitaxel
Can be used in Platinum-based chemotherapy regimen
Taxane
Carboplatin
Can be used as part of a platinum-based chemotherapy regimen
platinum containing compound (alkylating agent)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
ECOG PS 0 or 1
* Presence of at least 1 measurable lesion based on RECIST version 1.1 that has not been previously irradiated.
* Documentation of mutated KRAS gene
1. PDAC, CRC, Other tumor types: Confirmed KRAS mutation, any variant
2. NSCLC: Confirmed KRAS mutation, any variant except previously treated G12C. If driver mutation, must have failed precision medicine therapy \[eg, inhibitors of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and others\].
* Part 1 and Part 2a: Participant must have progressed on standard treatment(s) for which no additional, effective therapy is available.
1. 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.
2. 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.
3. 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;
4. 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.
* Part 2b:
1. 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.
2. 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.
3. 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.
4. NSCLC (1L) Cohort C2: Participants must have a TPS ≥50% and must not have received prior systemic treatment setting.
5. NSCLC (1L) Cohort C3: Participants with any TPS and must not have received prior systemic treatment setting.
Exclusion Criteria
* 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.
* Sensory peripheral neuropathy ≥Grade 2
* 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.
* Active bleeding disorder, including GI bleeding, as evidenced by hematemesis, significant hemoptysis or melena in the past 6 months.
* Major surgery or completion of radiation therapy ≤4 weeks prior to enrollment/randomization or radiation therapy that included \>30% of the bone marrow.
* 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)).
* Hematologic abnormalities.
* Renal impairment.
* Hepatic abnormalities.
18 Years
ALL
No
Sponsors
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Pfizer
INDUSTRY
Responsible Party
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Principal Investigators
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Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
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Highlands Oncology Group, PA
Fayetteville, Arkansas, United States
Highlands Oncology Group, PA
Rogers, Arkansas, 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
City of Hope Investigational Drug Service (IDS)
Duarte, California, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
Aurora, Colorado, 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
University of Colorado Hospital
Aurora, Colorado, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, United States
START Midwest
Grand Rapids, Michigan, United States
Siteman Cancer Center - St Peters
City of Saint Peters, Missouri, United States
Siteman Cancer Center - West County
Creve Coeur, Missouri, United States
Siteman Cancer Center - North County
Florissant, Missouri, United States
Siteman Cancer Center
St Louis, Missouri, United States
Barnes-Jewish Hospital
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center - South County
St Louis, Missouri, United States
Duke University Medical Center, lnvestigational Chemotherapy Service
Durham, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
West Chester Hospital
West Chester, Ohio, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Miriam 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
Countries
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Central Contacts
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Related Links
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To obtain contact information for a study center near you, click here.
Other Identifiers
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C5421001
Identifier Type: -
Identifier Source: org_study_id
NCT06447662
Identifier Type: REGISTRY
Identifier Source: secondary_id