Study of PF-07265807 in Participants With Metastatic Solid Tumors.

Pfizer

Status and phase: Terminated; Phase 1

Conditions: Neoplasm Metastasis

Treatments: Drug: Axitinib; Drug: Sasanlimab; Drug: PF-07265807

Study type: Interventional

Funder types: Industry

Identifiers

NCT04458259

C4201002

2021-004270-59 (EudraCT Number)

ARRAY-067-102 (Other Identifier)

Details and patient eligibility

About

A First-in-Human Pharmacokinetic, Safety, and Tolerability Study of PF-07265807 as Monotherapy and in Combination in Participants with Advanced or Metastatic Solid Tumors

Enrollment: 88 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• At least one measurable (Parts 1-4) or non-measurable lesion (Parts 1-3), not previously irradiated, as defined by RECIST 1.1
• ECOG Performance Status 0 or 1, 2 with approval
• Adequate Bone Marrow Function
• Adequate Renal Function
• Adequate Liver Function
• Resolved acute effects of any prior therapy
• Able to provide adequate archival tumor tissue or freshly obtained tumor tissue (some participants will require mandatory pre- and on-treatment biopsy is part of the biomarker cohort).
• Life expectancy of at least 3 months.
• Part 1 and Part 2: Participants who are intolerant or resistant to standard treatment for selected solid tumors.
• Part 3: Participants with advanced/metastatic RCC with a clear cell component and progressed with no standard therapy available.
• Part 4, Cohort 1: Participants with NSCLC with METex14-skipping alteration(s) and progressed on at least 1 prior therapy.
• Part 4, Cohort 2: Participants with MSS CRC with intermediate TMB and progressed with no satisfactory alternative treatment available, but has not received prior treatment with an anti-PD-(L)1 therapy.
• Part 4, Cohort 3: Participants with metastatic gastric or GEJ adenocarcinoma that is PD-L1 positive that has progressed on at least 2 but no more than 3 prior chemotherapy regiments, but has not received prior treatment with an anti-PD-(L)1 therapy.
• Part 4, Cohort 4: Participants with metastatic RCC with a clear cell component with IMDC intermediate or poor risk that have not received any prior systemic therapy for metastatic disease.

Exclusion criteria

• Known active uncontrolled or symptomatic CNS metastases.
• Any other active malignancy within 2 years prior to enrollment.
• Major surgery within 6 weeks, radiation therapy within 4 weeks, systemic anti-cancer therapy within 2 week or 5 half-lives (4 weeks or 5 half-lives for antibody therapies or investigational drug(s) taken on another study) prior to study entry.
• Active or history of autoimmune disease requiring >10mg/day prednisone or other concurrent immunosuppressive therapy.
• Active, uncontrolled infection (controlled HBV, HCV, HIV/AIDS may be allowed) as defined in protocol.
• Retinal or other serious ophthalmic disorders as defined in protocol.
• Clinically significant cardiac disease as defined in protocol.
• Uncontrolled HTN that cannot be controlled by medications.
• Inability to consume or absorb study drug.
• Known or suspected hypersensitivity to PF-07265807.
• Prohibited concomitant medications as defined in protocol.
• Active inflammatory GI disease, uncontrollable chronic diarrhea, or previous gastric resection or lap band surgery affecting absorption.
• Active bleeding disorder.
• Discontinuation of prior checkpoint inhibitor for treatment-related toxicity.
• Experienced >= G3 treatment-related irAE with prior PD-(L)1 agent.
• Prior treatment with selective AXL/MERTK inhibitors

For participants receiving sasanlimab:

- Known history of non-infectious pneumonitis that required steroid treatment or current pneumonitis.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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88 participants in 7 patient groups

Monotherapy Dose Escalation: Part 1

Experimental group

Description:

Monotherapy dose escalation of PF-07265807 in participants with select tumor types.

Treatment:

Drug: PF-07265807

Doublet Dose Escalation: Part 2

Experimental group

Description:

Doublet combination dose escalation of PF-07265807 with sasanlimab in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant.

Treatment:

Drug: PF-07265807

Drug: Sasanlimab

Triplet Dose Escalation: Part 3

Experimental group

Description:

Triplet combination dose escalation of PF-07265807 with sasanlimab plus axitinib in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Axitinib dose will follow label.

Treatment:

Drug: PF-07265807

Drug: Sasanlimab

Drug: Axitinib

Expansion Phase: Part 4, Cohort 1

Experimental group

Description:

PF-07265807 monotherapy in participants with METex14 mutant NSCLC.

Treatment:

Drug: PF-07265807

Expansion Phase: Part 4, Cohort 2

Experimental group

Description:

PF-07265807 with sasanlimab in participants with MSS CRC

Treatment:

Drug: PF-07265807

Drug: Sasanlimab

Expansion Phase: Part 4, Cohort 3

Experimental group

Description:

PF-07265807 with sasanlimab in participants with PD-L1+ gastric cancer/GEJ

Treatment:

Drug: PF-07265807

Drug: Sasanlimab

Expansion Phase: Part 4, Cohort 4

Experimental group

Description:

PF-07265807 with sasanlimab plus axitinib in participants with RCC

Treatment:

Drug: PF-07265807

Drug: Sasanlimab

Drug: Axitinib