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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.
NCT06447662 · Pfizer
In plain English
Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.
Official title
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
About this study
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.
Eligibility criteria
Inclusion Criteria:
* Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor.
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:
* 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.
* 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.
Study design
Enrollment target: 330 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-06-27
Estimated completion: 2028-09-09
Last updated: 2026-02-25
Interventions
Drug: PF-07934040Combination Product: GemcitabineCombination Product: Nab-paclitaxelCombination Product: CetuximabCombination Product: FluorouracilCombination Product: OxaliplatinCombination Product: LeucovorinCombination Product: BevacizumabCombination Product: PembrolizumabCombination Product: pemetrexedCombination Product: CisplatinCombination Product: PaclitaxelCombination Product: Carboplatin
Primary outcomes
- • 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))
- • 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)
- • Part 1: Number of participants with Dose-limiting toxicities (DLT) (Baseline up to 28 days)
Sponsor
Pfizer · industry
Contacts & investigators
ContactPfizer CT.gov Call Center · contact · ClinicalTrials.gov_Inquiries@pfizer.com · 1-800-718-1021
InvestigatorPfizer CT.gov Call Center · study_director, Pfizer
All locations (28)
Highlands Oncology Group, PARecruiting
Fayetteville, Arkansas, United States
Highlands Oncology Group, PARecruiting
Rogers, Arkansas, United States
Highlands Oncology GroupRecruiting
Springdale, Arkansas, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)Recruiting
Duarte, California, United States
City of Hope Investigational Drug Service (IDS)Recruiting
Duarte, California, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)Recruiting
Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Outpatient PavilionRecruiting
Aurora, Colorado, United States
University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)Recruiting
Aurora, Colorado, United States
University of Colorado HospitalRecruiting
Aurora, Colorado, United States
Sibley Memorial HospitalRecruiting
Washington D.C., District of Columbia, United States
START MidwestRecruiting
Grand Rapids, Michigan, United States
Siteman Cancer Center - St PetersRecruiting
City of Saint Peters, Missouri, United States
Siteman Cancer Center - West CountyRecruiting
Creve Coeur, Missouri, United States
Siteman Cancer Center - North CountyRecruiting
Florissant, Missouri, United States
Siteman Cancer CenterRecruiting
St Louis, Missouri, United States
Barnes-Jewish HospitalRecruiting
St Louis, Missouri, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Siteman Cancer Center - South CountyRecruiting
St Louis, Missouri, United States
Duke University Medical Center, lnvestigational Chemotherapy ServiceRecruiting
Durham, North Carolina, United States
Duke University Medical CenterRecruiting
Durham, North Carolina, United States
University of Cincinnati Medical CenterRecruiting
Cincinnati, Ohio, United States
Cleveland Clinic Taussig Cancer CenterRecruiting
Cleveland, Ohio, United States
West Chester HospitalRecruiting
West Chester, Ohio, United States
Rhode Island HospitalRecruiting
Providence, Rhode Island, United States
Miriam HospitalRecruiting
Providence, Rhode Island, United States
University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Beijing Cancer hospitalNot Yet Recruiting
Beijing, Beijing Municipality, China
Pan American Center for Oncology Trials, LLCRecruiting
Rio Piedras, Puerto Rico