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.

Launched by PFIZER · Jun 6, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called PF-07934040 to understand how safe it is and how well it works for people with advanced solid tumors that have a specific genetic change known as a KRAS mutation. This includes types of cancer like non-small cell lung cancer, colorectal cancer, and pancreatic cancer. The researchers want to determine the best dose of this medication, whether it works better on its own or when combined with other cancer treatments.

To participate, individuals should have advanced cancer that has not responded to standard treatments and must have a confirmed KRAS gene mutation. Participants will take PF-07934040 as a pill twice a day for 21 or 28-day cycles, and they may also receive other anti-cancer medications through an IV at the clinic. The study will last for up to four years, during which participants will have regular clinic visits to monitor their health and the effects of the treatment. This research aims to provide valuable information about new options for treating certain types of cancer.

Gender

ALL

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.