Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1

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

NCT ID: NCT06447662Sponsor: PfizerLast updated: 2026-04-20

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.

Arms & interventions

  • DrugPF-07934040

    panKRAS inhibitor

  • Combination ProductGemcitabine

    Chemotherapy (antimetabolite)

  • Combination ProductNab-paclitaxel

    Taxane-type Chemotherapy

  • Combination ProductCetuximab

    Monoclonal Antibody (EGFR Inhibitor)

  • Combination ProductFluorouracil

    Part of FOLFOX chemotherapy regimen cytotoxic chemotherapy (antimetabolite and pyrimidine analog)

  • Combination ProductOxaliplatin

    Part of FOLFOX Chemotherapy Regimen platinum based compound (alkylating agent)

  • Combination ProductLeucovorin

    Part of FOLFOX chemotherapy regimen Folic Acid Analog

  • Combination ProductBevacizumab

    VEG-F inhibitor

  • Combination ProductPembrolizumab

    immune checkpoint inhibitor (PD-1 inhibitor)

  • Combination Productpemetrexed

    Can be used in Platinum-based Chemotherapy regimen Antimetabolite

  • Combination ProductCisplatin

    Can be used as part of Platinum-based chemotherapy regimen Platinum-based antineoplastic (alkylating agent)

  • Combination ProductPaclitaxel

    Can be used in Platinum-based chemotherapy regimen Taxane

  • Combination ProductCarboplatin

    Can be used as part of a platinum-based chemotherapy regimen platinum containing compound (alkylating agent)

  • Combination ProductSasanlimab

    immune checkpoint inhibitor (PD-1 inhibitor)

Outcome measures

Primary

  • Part 1 & 2: Incidence of Adverse Events (AEs)

    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.

    Time frame: 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

    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).

    Time frame: 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)

    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

    Time frame: Baseline up to 28 days

  • Part 2: Objective Response - Number of Participants With Objective Response (alone or in combination)

    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.

    Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years'

Secondary

  • Part 1 & 2: Maximum Observed Serum Concentration (Cmax)

    Time frame: baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)

  • Part 1& 2: Time to Reach Maximum Observed Serum Concentration (Tmax)

    Time frame: Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)

  • Part 1 & 2: Serum Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

    Time frame: Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)

  • Part 1 & 2: Changes in pERK levels

    Time frame: Baseline through end of Cycle 1 (All cycles are 28 days except part 2b Cohort C2 which are 21 days)

  • Part 1: Objective Response - Number of Participants With Objective Response

    Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years

  • Part 1: Effect of Food on Cmax

    Time frame: Baseline through end of Cycle 1 (All cycles are 28 days)

  • Part 1: Effect of Food on Tmax

    Time frame: Baseline through end of Cycle 1 (All cycles are 28 days)

  • Part 1: Effect of Food on AUClast

    Time frame: Baseline through end of Cycle 1 (All cycles are 28 days)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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.

Study locations (26)

Highlands Oncology Group, PA

Fayetteville, Arkansas, 72703

Recruiting

Highlands Oncology Group, PA

Rogers, Arkansas, 72758

Recruiting

Highlands Oncology Group

Springdale, Arkansas, 72762

Recruiting

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, 91010

Recruiting

City of Hope Investigational Drug Service (IDS)

Duarte, California, 91010

Recruiting

University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)

Aurora, Colorado, 80045

Recruiting

University of Colorado Hospital - Anschutz Outpatient Pavilion

Aurora, Colorado, 80045

Recruiting

University of Colorado Hospital- Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, 80045

Recruiting

University of Colorado Hospital

Aurora, Colorado, 80045

Recruiting

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016

Recruiting

START Midwest

Grand Rapids, Michigan, 49546

Recruiting

Siteman Cancer Center - St Peters

City of Saint Peters, Missouri, 63376

Recruiting

Siteman Cancer Center - West County

Creve Coeur, Missouri, 63141

Recruiting

Siteman Cancer Center - North County

Florissant, Missouri, 63031

Recruiting

Siteman Cancer Center

St Louis, Missouri, 63108

Recruiting

Barnes-Jewish Hospital

St Louis, Missouri, 63110

Recruiting

Washington University School of Medicine

St Louis, Missouri, 63110

Recruiting

Siteman Cancer Center - South County

St Louis, Missouri, 63129

Recruiting

Duke University Medical Center, lnvestigational Chemotherapy Service

Durham, North Carolina, 27710

Recruiting

Duke University Medical Center

Durham, North Carolina, 27710

Recruiting

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219

Recruiting

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195

Recruiting

West Chester Hospital

West Chester, Ohio, 45069

Recruiting

Rhode Island Hospital

Providence, Rhode Island, 02903

Recruiting

Miriam Hospital

Providence, Rhode Island, 02906

Recruiting

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting