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

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.
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Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
230
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.
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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 abnormalities.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part 1 Dose EscalationPF-07985045PF-07985045 monotherapy Dose Escalation at prescribed dose and frequency in 28-day cycles
Part 1 Cohort A1PF-07985045PF-07985045 monotherapy dose expansion in 2-3L PDAC at prescribed dose and frequency in 28-day cycles
Part 1 Cohort B1PF-07985045PF-07985045 monotherapy dose expansion in 2-3L CRC at prescribed dose and frequency in 28-day cycles
Part 1 Cohort C1PF-07985045PF-07985045 monotherapy dose expansion in 2-3L NSCLC at prescribed dose and frequency in 28-day cycles
Part 1 Cohort D1PF-07985045PF-07985045 monotherapy dose expansion in other tumor types at prescribed dose and frequency in 28-day cycles
Part 2 Cohort A2PF-07985045Combination (PF-07985045 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles
Part 2 Cohort A2GemcitabineCombination (PF-07985045 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles
Part 2 Cohort A2Nab-paclitaxelCombination (PF-07985045 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B2PF-07985045Combination (PF-07985045 + Cetuximab) dose escalation/expansion in 2-3L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B2CetuximabCombination (PF-07985045 + Cetuximab) dose escalation/expansion in 2-3L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3PF-07985045Combination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3FluorouracilCombination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3OxaliplatinCombination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3LeucovorinCombination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort B3BevacizumabCombination (PF-07985045 + FOLFOX + Bevacizumab) dose escalation/ expansion in 1L CRC Prescribed dose and frequency in 28-day cycles
Part 2 Cohort C2PF-07985045Combination (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 C2PembrolizumabCombination (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 C2SasanlimabCombination (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 C3PF-07985045Combination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3PembrolizumabCombination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3pemetrexedCombination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3CisplatinCombination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3PaclitaxelCombination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort C3CarboplatinCombination (PF-07985045 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles
Part 2 Cohort XPF-07985045Combination (PF-07985045 + SHP2) dose escalation/expansion Prescribed dose and frequency in 21-day cycles
Part 2 Cohort XPF-07284892Combination (PF-07985045 + SHP2) dose escalation/expansion Prescribed dose and frequency in 21-day cycles
Primary Outcome Measures
NameTimeMethod
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 ...

PART 1 & 2: Number of participants with laboratory abnormalitiesFrom 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
NameTimeMethod
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 levelsBaseline 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 ResponseBaseline 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 CmaxBaseline 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 TmaxBaseline 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 AUClastBaseline through end of Cycle 1 (All cycles are 28 days)

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

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