A Study to Learn About the Study Medicine PF-07985045 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Change in a Gene.

May 19, 2026 updated by: Pfizer

A PHASE 1 OPEN-LABEL STUDY OF PF-07985045 AS A SINGLE-AGENT AND IN COMBINATION WITH OTHER ANTI-CANCER AGENTS IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

The purpose of this study is to learn about the safety and effects of the study medicine when given alone or together with other anti-cancer therapies. Anti-cancer therapy is a type of treatment to stop the growth of cancer.

This study also aims to find the best amount of study medication.

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-07985045) as pill by mouth. This will be repeated 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-07985045 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 different times (depending on the treatment) during the 21-day or 28-day cycle.

Participants can continue to take the study medication (PF-07985045) 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 in this study for up to 4 years. During this time, the participants will come into the clinic for 1 to 4 times in each 21-day or 28-day cycle. After the participants 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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • Rio Piedras, Puerto Rico, 00935
        • Pan American Center for Oncology Trials, LLC
  • United States
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group
      • Rogers, Arkansas, United States, 72758
        • Highlands Oncology Group
      • Springdale, Arkansas, United States, 72762
        • Highlands Oncology Group
    • California
      • Duarte, California, United States, 91010
        • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Newton, Massachusetts, United States, 02467
        • DFCI Chestnut Hill
    • New York
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center
      • New York, New York, United States, 10032
        • The Trustees of Columbia University and The New York and Presbyterian Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53718
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center-University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histological or cytological diagnosis of advanced, unresectable, and/or metastatic or relapsed/refractory solid tumor.

    • Note for PDAC: Only participants with the histologic type of adenocarcinoma of the pancreas are allowed to enroll. For PDAC, if loco-regional disease is present, must also have metastatic disease.
    • Note for NSCLC: If a driver mutation is present, the participant was resistant or intolerant of precision medicine therapy (eg, inhibitors of EGFR, ALK, ROS1, or others).
  • 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

    a. KRAS mutations of any variant except previously treated with any KRAS inhibitor

  • Part 1: 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/or 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 only 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 2:

    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 pneumonitis/ILD, pulmonary fibrosis requiring treatment with systemic steroid therapy. Additionally, participants in IO combinations (Cohorts C2 and C3) with history and/or active pneumonitis/ILD or pulmonary fibrosis requiring steroids are excluded from enrollment.
  • 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.
  • Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including drainage catheter placement, therapeutic thoracentesis or abdominal paracentesis) is eligible.
  • Current use or have received PPIs in the last seven days prior to starting study treatment.
  • Known sensitivity or contraindication to any component of study intervention (PF-07985045, gemcitabine, nab-paclitaxel, cetuximab, bevacizumab, FOLFOX, 5-FU, pembrolizumab, sasanlimab, cisplatin, carboplatin, pemetrexed, SHP2 inhibitor(s).
  • Hematologic abnormalities.
  • Renal impairment.
  • Hepatic abnormalities.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 Dose Escalation
PF-07985045 monotherapy Dose Escalation at prescribed dose and frequency in 28-day cycles
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 1 Cohort A1
PF-07985045 monotherapy dose expansion in 2-3L PDAC at prescribed dose and frequency in 28-day cycles
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 1 Cohort B1
PF-07985045 monotherapy dose expansion in 2-3L CRC at prescribed dose and frequency in 28-day cycles
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 1 Cohort C1
PF-07985045 monotherapy dose expansion in 2-3L NSCLC at prescribed dose and frequency in 28-day cycles
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 1 Cohort D1
PF-07985045 monotherapy dose expansion in other tumor types at prescribed dose and frequency in 28-day cycles
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 2 Cohort A2

Combination (PF-07985045 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC.

Prescribed dose and frequency in 28-day cycles
Combination product: Gemcitabine
Chemotherapy (antimetabolite)
Other Names:
  • Gemzar
Combination product: Nab-paclitaxel
Taxane-type Chemotherapy
Other Names:
  • Abraxane
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 2 Cohort B2

Combination (PF-07985045 + Cetuximab) dose escalation/expansion in 2-3L CRC

Prescribed dose and frequency in 28-day cycles
Combination product: Cetuximab
Monoclonal Antibody (EGFR Inhibitor)
Other Names:
  • Erbitux
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 2 Cohort B3

Combination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC

Prescribed dose and frequency in 28-day cycles
Combination product: Fluorouracil

Part of FOLFOX chemotherapy regimen

cytotoxic chemotherapy (antimetabolite and pyrimidine analog)

Other Names:
  • 5-FU
  • 5-fluorouracil
Combination product: Oxaliplatin

Part of FOLFOX Chemotherapy Regimen

platinum based compound (alkylating agent)

Other Names:
  • Eloxatin
Combination product: Leucovorin

Part of FOLFOX chemotherapy regimen

Folic Acid Analog

Other Names:
  • Wellcovorin
  • Folinic Acid
  • calcium folinate
  • Leucovorin Calcium
Combination product: Bevacizumab
VEG-F inhibitor
Other Names:
  • Avastin
  • Zirabev
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 2 Cohort C2

Combination (PF-07985045 + Pembro or sasanlimab) dose escalation/expansion in 1L NSCLC (TPS ≥ 50%)

Prescribed dose and frequency in 21-day (pembro) or 28-day (sasanlimab) cycles
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Combination product: Pembrolizumab
immune checkpoint inhibitor (PD-1 inhibitor
Other Names:
  • Keytruda
  • MK-3475
  • Lambrolizumab
  • Pembro
Combination product: Sasanlimab
immune checkpoint inhibitor (PD-1 inhibitor)
Other Names:
  • PF-06801591
Experimental: Part 2 Cohort C3

Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS)

Prescribed dose and frequency in 21-day cycles
Combination product: pemetrexed

Can be used in Platinum-based Chemotherapy regimen

Antimetabolite

Other Names:
  • Alimta
Combination product: Cisplatin

Can be used as part of Platinum-based chemotherapy regimen

Platinum-based antineoplastic (alkylating agent)

Other Names:
  • Cisplatinum
  • Platinol
  • neoplatin
Combination product: Paclitaxel

Can be used in Platinum-based chemotherapy regimen

Taxane

Other Names:
  • Taxol
  • Onxol
Combination product: Carboplatin

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

platinum containing compound (alkylating agent)

Other Names:
  • Paraplatin
  • Stricarb
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Combination product: Pembrolizumab
immune checkpoint inhibitor (PD-1 inhibitor
Other Names:
  • Keytruda
  • MK-3475
  • Lambrolizumab
  • Pembro
Experimental: Part 2 Cohort B4

Combination (PF-07985045 + FOLFOX + Cetuximab) dose escalation/ expansion in 1L CRC

Prescribed dose and frequency in 28-day cycles
Combination product: Cetuximab
Monoclonal Antibody (EGFR Inhibitor)
Other Names:
  • Erbitux
Combination product: Fluorouracil

Part of FOLFOX chemotherapy regimen

cytotoxic chemotherapy (antimetabolite and pyrimidine analog)

Other Names:
  • 5-FU
  • 5-fluorouracil
Combination product: Oxaliplatin

Part of FOLFOX Chemotherapy Regimen

platinum based compound (alkylating agent)

Other Names:
  • Eloxatin
Combination product: Leucovorin

Part of FOLFOX chemotherapy regimen

Folic Acid Analog

Other Names:
  • Wellcovorin
  • Folinic Acid
  • calcium folinate
  • Leucovorin Calcium
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Experimental: Part 2 Cohort X

Combination (PF-07985045 + PF-07284892) dose escalation/expansion

Prescribed dose and frequency in 21-day cycles
Drug: PF-07985045
KRAS inhibitor
Other Names:
  • PF-5045
Combination product: PF-07284892
PF-07284892 used as a combination product.
Other Names:
  • ARRY-558

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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).
From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first
Part 1 & Part 2 (Dose Escalation Only): 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
Baseline up to 28 days
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) assessed by the Investigator.
Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion, approximately 2 years'

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1 & 2: Maximum Observed Serum Concentration (Cmax)
Time Frame: baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 which are 21 days)
Evaluate the single and multiple dose PK ofPF-07985045 as monotherapy, or in combination with other anti-tumor agents.
baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 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 2 Cohort C2/C3 which are 21 days)
Evaluate the single and multiple dose PK of PF-07985045 as monotherapy, or in combination with other anti-tumor agents.
Baseline through end of Cycle 1 (All cycles are 28 days except part 2 Cohort C2/C3 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 2 Cohort C2/C3 which are 21 days)
Evaluate the single and multiple dose PK of PF-07985045 as monotherapy, or in combination with other anti-tumor agents.
Baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 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 2 Cohort C2/C3 which are 21 days)
Evaluates the intended mechanism of action (MoA) modulation of KRAS inhibition and target engagement effect of PF-07985045 in peripheral blood of participants with advanced solid tumor malignancies.
Baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 which are 21 days)
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) (Part 1 only), progression free survival (PFS), and duration of response (DOR).
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)
Evaluate the effect of food on Cmax of PF-07985045 as monotherapy.
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)
Evaluate the effect of food on Tmax of PF-07985045 as monotherapy.
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)
Evaluate the effect of food on AUClast of PF-07985045 as monotherapy.
Baseline through end of Cycle 1 (All cycles are 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 10, 2024

Primary Completion (Actual)

May 12, 2026

Study Completion (Actual)

May 12, 2026

Study Registration Dates

First Submitted

November 21, 2024

First Submitted That Met QC Criteria

November 21, 2024

First Posted (Actual)

November 26, 2024

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 19, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C6081001
  • 2024-517988-23-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carcinoma, Non-Small-Cell Lung

Clinical Trials on Gemcitabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malta

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe