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.

NCT06704724 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: C60810012024-517988-23-00
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 13

Brief Summary

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

Conditions

Carcinoma, Pancreatic Ductal; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung

Keywords

Carcinoma, Pancreatic Ductal; Carcinoma, Ductal, Pancreatic; Duct-Cell Carcinoma of the Pancreas; Duct-Cell Carcinoma, Pancreas; Ductal Carcinoma of the Pancreas; Pancreatic Duct Cell Carcinoma; Pancreatic Ductal Carcinoma; pancreatic ductal adenocarcinoma; PDAC; Colorectal Neoplasms; Colorectal Cancer; Colorectal Carcinoma; Colorectal Tumors; Neoplasms, Colorectal; Rectal Cancer; Colon Cancer; CRC; MSS CRC; Carcinoma, Non-Small-Cell Lung; Non-Small Cell Lung Cancer; Non-Small Cell Lung Carcinoma; Non-Small-Cell Lung Carcinoma; Nonsmall Cell Lung Cancer; Lung Cancer; NSCLC; KRAS; KRAS gene mutation

Outcome Measures

Primary Outcomes (4)

• 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.

  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).

  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)

  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)

  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 Outcomes (8)

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

  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)

  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)

  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

  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

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

Study Arms (12)

Part 1 Dose Escalation

EXPERIMENTAL

PF-07985045 monotherapy Dose Escalation at prescribed dose and frequency in 28-day cycles

Drug: PF-07985045

Part 1 Cohort A1

EXPERIMENTAL

PF-07985045 monotherapy dose expansion in 2-3L PDAC at prescribed dose and frequency in 28-day cycles

Drug: PF-07985045

Part 1 Cohort B1

EXPERIMENTAL

PF-07985045 monotherapy dose expansion in 2-3L CRC at prescribed dose and frequency in 28-day cycles

Drug: PF-07985045

Part 1 Cohort C1

EXPERIMENTAL

PF-07985045 monotherapy dose expansion in 2-3L NSCLC at prescribed dose and frequency in 28-day cycles

Drug: PF-07985045

Part 1 Cohort D1

EXPERIMENTAL

PF-07985045 monotherapy dose expansion in other tumor types at prescribed dose and frequency in 28-day cycles

Drug: PF-07985045

Part 2 Cohort A2

EXPERIMENTAL

Combination (PF-07985045 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles

Drug: PF-07985045; Combination Product: Gemcitabine; Combination Product: Nab-paclitaxel

Part 2 Cohort B2

EXPERIMENTAL

Combination (PF-07985045 + Cetuximab) dose escalation/expansion in 2-3L CRC Prescribed dose and frequency in 28-day cycles

Drug: PF-07985045; Combination Product: Cetuximab

Part 2 Cohort B3

EXPERIMENTAL

Combination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles

Drug: PF-07985045; Combination Product: Fluorouracil; Combination Product: Oxaliplatin; Combination Product: Leucovorin; Combination Product: Bevacizumab

Part 2 Cohort B4

EXPERIMENTAL

Combination (PF-07985045 + FOLFOX + Cetuximab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles

Drug: PF-07985045; Combination Product: Cetuximab; Combination Product: Fluorouracil; Combination Product: Oxaliplatin; Combination Product: Leucovorin

Part 2 Cohort C2

EXPERIMENTAL

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; Combination Product: Pembrolizumab; Combination Product: Sasanlimab

Part 2 Cohort C3

EXPERIMENTAL

Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles

Drug: PF-07985045; Combination Product: Pembrolizumab; Combination Product: pemetrexed; Combination Product: Cisplatin; Combination Product: Paclitaxel; Combination Product: Carboplatin

Part 2 Cohort X

EXPERIMENTAL

Combination (PF-07985045 + PF-07284892) dose escalation/expansion Prescribed dose and frequency in 21-day cycles

Drug: PF-07985045; Combination Product: PF-07284892

Interventions

PF-07985045 DRUG

KRAS inhibitor

Also known as: PF-5045

Part 1 Cohort A1; Part 1 Cohort B1; Part 1 Cohort C1; Part 1 Cohort D1; Part 1 Dose Escalation; Part 2 Cohort A2; Part 2 Cohort B2; Part 2 Cohort B3; Part 2 Cohort B4; Part 2 Cohort C2; Part 2 Cohort C3; Part 2 Cohort X

Gemcitabine COMBINATION_PRODUCT

Chemotherapy (antimetabolite)

Also known as: Gemzar

Part 2 Cohort A2

Nab-paclitaxel COMBINATION_PRODUCT

Taxane-type Chemotherapy

Also known as: Abraxane

Part 2 Cohort A2

Cetuximab COMBINATION_PRODUCT

Monoclonal Antibody (EGFR Inhibitor)

Also known as: Erbitux

Part 2 Cohort B2; Part 2 Cohort B4

Fluorouracil COMBINATION_PRODUCT

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

Also known as: 5-FU, 5-fluorouracil

Part 2 Cohort B3; Part 2 Cohort B4

Oxaliplatin COMBINATION_PRODUCT

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

Also known as: Eloxatin

Part 2 Cohort B3; Part 2 Cohort B4

Leucovorin COMBINATION_PRODUCT

Part of FOLFOX chemotherapy regimen Folic Acid Analog

Also known as: Folinic Acid, Wellcovorin, calcium folinate, Leucovorin Calcium

Part 2 Cohort B3; Part 2 Cohort B4

Bevacizumab COMBINATION_PRODUCT

VEG-F inhibitor

Also known as: Zirabev, Avastin

Part 2 Cohort B3

Pembrolizumab COMBINATION_PRODUCT

immune checkpoint inhibitor (PD-1 inhibitor

Also known as: Pembro, Lambrolizumab, MK-3475, Keytruda

Part 2 Cohort C2; Part 2 Cohort C3

Sasanlimab COMBINATION_PRODUCT

immune checkpoint inhibitor (PD-1 inhibitor)

Also known as: PF-06801591

Part 2 Cohort C2

pemetrexed COMBINATION_PRODUCT

Can be used in Platinum-based Chemotherapy regimen Antimetabolite

Also known as: Alimta

Part 2 Cohort C3

Cisplatin COMBINATION_PRODUCT

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

Also known as: Platinol, Cisplatinum, neoplatin

Part 2 Cohort C3

Paclitaxel COMBINATION_PRODUCT

Can be used in Platinum-based chemotherapy regimen Taxane

Also known as: Taxol, Onxol

Part 2 Cohort C3

Carboplatin COMBINATION_PRODUCT

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

Also known as: Paraplatin, Stricarb

Part 2 Cohort C3

PF-07284892 COMBINATION_PRODUCT

PF-07284892 used as a combination product.

Also known as: ARRY-558

Part 2 Cohort X

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 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.
• 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.
• 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:
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (13)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

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

Duarte, California, 91010, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

DFCI Chestnut Hill

Newton, Massachusetts, 02467, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

The Trustees of Columbia University and The New York and Presbyterian Hospital

New York, New York, 10032, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin, 53718, United States

Location

University of Wisconsin Carbone Cancer Center-University Hospital

Madison, Wisconsin, 53792, United States

Location

Pan American Center for Oncology Trials, LLC

Rio Piedras, 00935, Puerto Rico

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Carcinoma, Pancreatic Ductal; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Rectal Neoplasms; Colonic Neoplasms; Lung Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Cetuximab; Fluorouracil; Oxaliplatin; Leucovorin; Bevacizumab; pembrolizumab; Pemetrexed; Cisplatin; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: November 26, 2024
• Study Start: December 10, 2024
• Primary Completion (Estimated): March 11, 2028
• Study Completion (Estimated): March 11, 2029
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); PR (1)