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Investigating PF-07934040 for advanced solid tumors with genetic mutations

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

Phase 1 Interventional Pfizer · NCT06447662

This study is testing a new drug called PF-07934040 to see if it can safely help people with advanced solid tumors that have a KRAS gene mutation, including tough-to-treat cancers like lung, colorectal, and pancreatic cancer.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment330 (estimated)
Ages18 Years and up
SexAll
SponsorPfizer Industry-sponsored
Drugs / interventionscetuximab, bevacizumab, pembrolizumab, chemotherapy, immunotherapy, radiation, prednisone
Locations28 sites (Fayetteville, Arkansas and 27 other locations)
Trial IDNCT06447662 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and efficacy of the investigational drug PF-07934040, both alone and in combination with other anti-cancer therapies, in patients with advanced solid tumors that have a KRAS gene mutation. Participants will be monitored for the drug's effects and the optimal dosage will be determined. The study focuses on specific cancer types, including non-small cell lung cancer, colorectal cancer, and pancreatic ductal adenocarcinoma, which are known to be challenging to treat.

Who should consider this trial

Good fit: Ideal candidates include individuals with advanced, unresectable solid tumors that have a confirmed KRAS gene mutation.

Not a fit: Patients without a KRAS mutation or those with early-stage tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors that harbor KRAS mutations.

How similar studies have performed: Other studies targeting KRAS mutations have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion 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 or ICI. Participants may have had only one or two prior lines of therapy in the advanced/metastatic setting. 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 lines of therapy for mCRC. For either one or two prior treatments, these regimens must have included a fluoropyrimidine, oxaliplatin, and/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. If relapse occurred within 6 months of last dose of adjuvant treatment or neoadjuvant 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/B4: Participants must not have received prior therapy for metastatic disease and not be a candidate for other targeted therapy or immunotherapy. Participant could have received neoadjuvant therapy, adjuvant therapy, or adjuvant chemo-radiotherapy. If relapse occurred within 6 months of last dose of adjuvant or neoadjuvant therapy, then 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 or pulmonary fibrosis requiring treatment with systemic steroid therapy.
* 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.

Where this trial is running

Fayetteville, Arkansas and 27 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Carcinoma, Pancreatic DuctalColorectal NeoplasmsCarcinoma, Non-Small-Cell LungCarcinoma, Ductal, PancreaticDuct-Cell Carcinoma of the PancreasDuct-Cell Carcinoma, PancreasDuctal Carcinoma of the PancreasPancreatic Duct Cell Carcinoma
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.