NCT04881045 - Study to Test the Safety and Tolerability of PF-07257876 in Participants With Selected Advanced Tumors. | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histological/cytological diagnosis of selected advanced or metastatic tumor * Prior treatment with PD-1 (Programmed cell death 1) or PD-L1 (programmed death-ligand 1) in NSCLC and SCCHN or platinum-based therapy in Ovarian cancer * Confirmed radiographic progression of disease * PD-L1 IHC positivity ≥1% * Have ≥1 measurable lesion as defined by RECIST 1.1 that has not been previously irradiated * Eastern Cooperative Oncology Group performance status 0-1 * Adequate hematologic, renal and liver functions * Resolved acute effects of any prior therapy * Participants in Part 1 must be able to provide archival tumor tissue collected within the prior 6 months or consent to undergo a fresh biopsy during screening. Participants enrolled to the MTD (Maximum Tolerated Dose) cohort in Part 1 must consent to mandatory paired pre-treatment and on-treatment biopsies. Participants in Part 2 must consent to a pre-treatment biopsy and a subset of patients must consent to a paired on-study biopsy as well until the Sponsor deems an adequate number have been received. Exclusion Criteria: * Participants with known brain metastasis larger than 4 cm or that is symptomatic. New brain metastases detected at screening. Participants with previously diagnosed brain metastases are eligible if they have completed treatment and recovered from acute effects prior to study entry. * Abnormal neurological assessment by investigator * Other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ * Major surgery or radiation therapy within 4 weeks prior to planned first dose * Last systemic anti-cancer therapy within 28 days or 5 half-lives (whichever is shorter) prior to planned first dose (6 weeks for mitomycin C or nitrosoureas) * Active bleeding disorder in the past 6 months prior to first dose * History of clinically significant severe immune mediated adverse event that was considered related to prior immune modulatory therapy and required immunosuppressive therapy (other than hormone replacement therapy) * History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (ie, bronchiolitis obliterans, cryptogenic organizing pneumonia), evidence of active pneumonitis on screening chest CT(computer tomography) scan * Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed * Treatment with chronic systemic corticosteroids or other immunosuppressive medications * Participation in other studies involving investigational drug(s) within 4 weeks prior to planned first dose * Active, uncontrolled bacterial, fungal, or viral infection, Hepatitis B, Hepatitis C, or Human immunodeficiency virus (HIV) infection * Active COVID-19/SARS-CoV2 * Pregnant or breastfeeding female participant * Organ transplant requiring immunosuppressive treatment or prior allogeneic bone marrow or hematopoietic stem cell transplant * Significant cardiac or pulmonary conditions or events within previous 6 months

Outcomes

Primary Outcomes

Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1)

DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose

Time frame: Baseline through end of Cycle 1 (each cycle is 28 days)

Number of participants with adverse events (AEs)

AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 5.0), timing, seriousness, and relationship to study therapy.

Time frame: Baseline through up to 2 years

Number of participants with clinically significant laboratory abnormalities

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Time frame: Baseline through up to 2 years

Objective response rate (ORR) in the Expansion cohorts (Part 2)

Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Time frame: Baseline through up to 2 years or until disease progression