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The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

Category

Other or Multiple Cancer Types

KRAS Inhibitor

PF-07985045 is an investigational compound. Its safety and efficacy have not been established

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

Phase 1

NCT06704724

Active enrolling

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Locations

United States, Puerto Rico

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Study design
Participant Group/Arm

EXPERIMENTAL: Part 1 Dose Escalation

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

EXPERIMENTAL: Part 1 Cohort A1

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

EXPERIMENTAL: Part 1 Cohort B1

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

EXPERIMENTAL: Part 1 Cohort C1

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

EXPERIMENTAL: Part 1 Cohort D1

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

EXPERIMENTAL: Part 2 Cohort B2

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

EXPERIMENTAL: Part 2 Cohort B3

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

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

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Participant Group/Arm

EXPERIMENTAL: Part 2 Cohort X

Combination (PF-07985045 + SHP2) dose escalation/expansion Prescribed dose and frequency in 21-day cycles

Intervention/Treatment

DRUG: PF-07985045

KRAS inhibitor

Study design table for Clinical Trial
Key eligibility criteria
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 not previously treated G12C, present in tumor tissue or blood 2. If the participant received any RAS or KRAS inhibitor treatment previously, a new KRAS mutation must be other than the original mutation treated.
  • 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 neoadjuvant or 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 neoadjuvant or 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 that required or is 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 (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 abnormalitie
Key dates
Study start date
  • December 2024
Estimated Study Completion Date
  • January 2029
Key endpoints
Primary Outcome Measures
Outcome Measure

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

Measure Description

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)

Outcome Measure

PART 1 & 2: Number of participants with laboratory abnormalities

Measure Description

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

Outcome Measure

Part 1 & Part 2 (Dose Escalation Only): Number of participants with Dose-limiting toxicities (DLT)

Measure Description

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

Outcome Measure

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

Measure Description

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.

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'

Primary Outcome Measures table for Clinical Trial
Secondary Outcome Measures:
Outcome Measure

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

Measure Description

Evaluate the single and multiple dose PK ofPF-07985045 as monotherapy, or in combination with other anti-tumor agents.

Time Frame

baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 which are 21 days)

Outcome Measure

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

Measure Description

Evaluate the single and multiple dose PK of PF-07985045 as monotherapy, or in combination with other anti-tumor agents.

Time Frame

Baseline through end of Cycle 1 (All cycles are 28 days except part 2 Cohort C2/C3 which are 21 days)

Outcome Measure

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

Measure Description

Evaluate the single and multiple dose PK of PF-07985045 as monotherapy, or in combination with other anti-tumor agents.

Time Frame

Baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 which are 21 days)

Outcome Measure

Part 1 & 2: Changes in pERK levels

Measure Description

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.

Time Frame

Baseline through end of Cycle 1 (All cycles are 28 days except Part 2 Cohort C2/C3 which are 21 days)

Outcome Measure

Objective Response - Number of Participants With Objective Response

Measure Description

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).

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

Outcome Measure

Part 1: Effect of Food on Cmax

Measure Description

Evaluate the effect of food on Cmax of PF-07985045 as monotherapy.

Time Frame

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

Outcome Measure

Part 1: Effect of Food on Tmax

Measure Description

Evaluate the effect of food on Tmax of PF-07985045 as monotherapy.

Time Frame

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

Outcome Measure

Part 1: Effect of Food on AUClast

Measure Description

Evaluate the effect of food on AUClast of PF-07985045 as monotherapy.

Time Frame

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

Secondary Outcome Measures table for Clinical Trial
Number of participants

190

Collaborators and investigators

Sponsor: Pfizer

Collaborator: None

This information is current as of March 25th 2025.

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When calling, please reference this study number:

More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT06704724