Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT06447662

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.

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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
  • PDAC, CRC, Other tumor types: Confirmed KRAS mutation, any variant
  • 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.
  • 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.
  • 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.
  • 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;
  • 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:
  • 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.
  • 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.
  • 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.
  • NSCLC (1L) Cohort C2: Participants must have a TPS ≥50% and must not have received prior systemic treatment setting.
  • 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.

Treatment and study plan

PF-07934040

Drug

panKRAS inhibitor

Other names: PF-4040

Gemcitabine

Combination Product

Chemotherapy (antimetabolite)

Other names: Gemzar

Nab-Paclitaxel

Combination Product

Taxane-type Chemotherapy

Other names: Abraxane

Cetuximab

Combination Product

Monoclonal Antibody (EGFR Inhibitor)

Other names: Erbitux

Fluorouracil

Combination Product

Part of FOLFOX chemotherapy regimen

cytotoxic chemotherapy (antimetabolite and pyrimidine analog)

Other names: 5-FU, 5-fluorouracil

Oxaliplatin

Combination Product

Part of FOLFOX Chemotherapy Regimen

platinum based compound (alkylating agent)

Other names: Eloxatin

Leucovorin

Combination Product

Part of FOLFOX chemotherapy regimen

Folic Acid Analog

Other names: Folinic Acid, Wellcovorin, calcium folinate, Leucovorin Calcium

Bevacizumab

Combination Product

VEG-F inhibitor

Other names: Zirabev, Avastin

Pembrolizumab

Combination Product

immune checkpoint inhibitor (PD-1 inhibitor)

Other names: Pembro, Lambrolizumab, MK-3475, Keytruda

pemetrexed

Combination Product

Can be used in Platinum-based Chemotherapy regimen

Antimetabolite

Other names: Alimta

Cisplatin

Combination Product

Can be used as part of Platinum-based chemotherapy regimen

Platinum-based antineoplastic (alkylating agent)

Other names: Platinol, Cisplatinum, neoplatin

Paclitaxel

Combination Product

Can be used in Platinum-based chemotherapy regimen

Taxane

Other names: Taxol, Onxol

Carboplatin

Combination Product

Can be used as part of a platinum-based chemotherapy regimen

platinum containing compound (alkylating agent)

Other names: Paraplatin, Stricarb

Sasanlimab

Combination Product

immune checkpoint inhibitor (PD-1 inhibitor)

Other names: PF-06081591

Primary outcomes

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

    Time frame: Start of treatment up to 30 days after last dose or start of new anticancer therapy (whichever occurs first)

    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.

  2. PART 1 & 2: Number of participants with laboratory abnormalities

    Time frame: From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first

    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).

  3. Part 1: Number of participants with Dose-limiting toxicities (DLT)

    Time frame: Baseline up to 28 days

    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

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

    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'

    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.

Secondary outcomes

  1. 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)

    Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.

  2. 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)

    Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.

  3. 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)

    Evaluate the single and multiple dose PK of PF-07934040 as monotherapy, or in combination with other anti-tumor agents.

  4. 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)

    Evaluates the intended mechanism of action (MoA) modulation of KRAS inhibition and target engagement effect of PF-07934040 in peripheral blood of participants with advanced solid tumor malignancies.

  5. 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

    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) assessed by the Investigator including overall response rate (ORR), progression free survival (PFS), and overall survival (OS).

  6. Part 1: Effect of Food on Cmax

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

    Evaluate the effect of food on Cmax of PF-07934040 as monotherapy.

  7. Part 1: Effect of Food on Tmax

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

    Evaluate the effect of food on Tmax of PF-07934040 as monotherapy.

  8. Part 1: Effect of Food on AUClast

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

    Evaluate the effect of food on AUClast of PF-07934040 as monotherapy.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jun 7, 2024
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.