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.

Phase 1

Recruiting

• Conditions: Carcinoma, Pancreatic Ductal; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: PF-07985045; Combination Product: Gemcitabine; Combination Product: Cetuximab; Combination Product: Fluorouracil; Combination Product: Pembrolizumab; Combination Product: PF-07284892; Combination Product: Nab-paclitaxel; Combination Product: Oxaliplatin; Combination Product: Sasanlimab; Combination Product: pemetrexed; Combination Product: Leucovorin; Combination Product: Cisplatin; Combination Product: Bevacizumab; Combination Product: Paclitaxel; Combination Product: Carboplatin

• Registration Number: NCT06704724
• Lead Sponsor: Pfizer

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 once a day. 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-21
• Study First Submitted QC: 2024-11-21
• Study First Posted: 2024-11-26
• Study Start: 2024-12-10
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-15
• Last Update Posted: 2025-05-16
• Primary Completion: 2028-01-09
• Study Completion: 2029-01-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 190

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

  1. KRAS mutations of any variant except previously treated G12C, present in tumor tissue or blood
  2. If the participant received KRAS G12C inhibitor treatment previously, the KRAS mutation status must be other than G12C

• 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 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 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 or history of pneumonitis/ILD, pulmonary fibrosis requiring treatment with systemic steroid therapy, including evidence to suggest pneumonitis/ILD on baseline assessments including imaging.

• 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 (Part 2 only)

• 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-07985045, gemcitabine, nab-paclitaxel, cetuximab, bevacizumab, FOLFOX, 5-FU, pembrolizumab, sasanlimab, cisplatin, carboplatin, pemetrexed, SHP2 inhibitor(s).

• Hematologic abnormalities.

• Renal impairment.

  • Hepatic abnormalities.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 Dose Escalation	PF-07985045	PF-07985045 monotherapy Dose Escalation at prescribed dose and frequency in 28-day cycles
Part 1 Cohort A1	PF-07985045	PF-07985045 monotherapy dose expansion in 2-3L PDAC at prescribed dose and frequency in 28-day cycles
Part 1 Cohort B1	PF-07985045	PF-07985045 monotherapy dose expansion in 2-3L CRC at prescribed dose and frequency in 28-day cycles
Part 1 Cohort C1	PF-07985045	PF-07985045 monotherapy dose expansion in 2-3L NSCLC at prescribed dose and frequency in 28-day cycles
Part 1 Cohort D1	PF-07985045	PF-07985045 monotherapy dose expansion in other tumor types at prescribed dose and frequency in 28-day cycles
Part 2 Cohort A2	PF-07985045	Combination (PF-07985045 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles
Part 2 Cohort A2	Gemcitabine	Combination (PF-07985045 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles
Part 2 Cohort A2	Nab-paclitaxel	Combination (PF-07985045 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B2	PF-07985045	Combination (PF-07985045 + Cetuximab) dose escalation/expansion in 2-3L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B2	Cetuximab	Combination (PF-07985045 + Cetuximab) dose escalation/expansion in 2-3L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3	PF-07985045	Combination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3	Fluorouracil	Combination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3	Oxaliplatin	Combination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3	Leucovorin	Combination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3	Bevacizumab	Combination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort C2	PF-07985045	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
Part 2 Cohort C2	Pembrolizumab	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
Part 2 Cohort C2	Sasanlimab	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
Part 2 Cohort C3	PF-07985045	Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3	Pembrolizumab	Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3	pemetrexed	Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3	Cisplatin	Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3	Paclitaxel	Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3	Carboplatin	Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort X	PF-07985045	Combination (PF-07985045 + SHP2) dose escalation/expansion Prescribed dose and frequency in 21-day cycles
Part 2 Cohort X	PF-07284892	Combination (PF-07985045 + SHP2) dose escalation/expansion Prescribed dose and frequency in 21-day cycles

Primary Outcome Measures

Name	Time	Method
Part 1 & 2: Incidence of Adverse Events (AEs)	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.
PART 1 & 2: Number of participants with laboratory abnormalities	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).
Part 1 & Part 2 (Dose Escalation Only): Number of participants with Dose-limiting toxicities (DLT)	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
Part 2: Objective Response - Number of Participants With Objective Response (alone or in combination)	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.

Secondary Outcome Measures

Name	Time	Method
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)	Evaluate the single and multiple dose PK ofPF-07985045 as monotherapy, or in combination with other anti-tumor agents.
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)	Evaluate the single and multiple dose PK of PF-07985045 as monotherapy, or in combination with other anti-tumor agents.
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)	Evaluate the single and multiple dose PK of PF-07985045 as monotherapy, or in combination with other anti-tumor agents.
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)	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.
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	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).
Part 1: Effect of Food on Cmax	Baseline through end of Cycle 1 (All cycles are 28 days)	Evaluate the effect of food on Cmax of PF-07985045 as monotherapy.
Part 1: Effect of Food on Tmax	Baseline through end of Cycle 1 (All cycles are 28 days)	Evaluate the effect of food on Tmax of PF-07985045 as monotherapy.
Part 1: Effect of Food on AUClast	Baseline through end of Cycle 1 (All cycles are 28 days)	Evaluate the effect of food on AUClast of PF-07985045 as monotherapy.

Trial Locations

Locations (8)

Highlands Oncology Group; 🇺🇸 Springdale, Arkansas, United States

City of Hope (City of Hope National Medical Center, City Of Hope Medical Center); 🇺🇸 Duarte, California, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

DFCI Chestnut Hill; 🇺🇸 Newton, Massachusetts, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Pan American Center for Oncology Trials, LLC; 🇵🇷 Rio Piedras, Puerto Rico