MC# 22-29 - A Phase I, Open-Label, Dose Escalation and Expansion Study of PF-07265028 as a Single Agent and in Combination with Sasanlimab Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of PF-07265028 in Participants with Advanced or Metastatic Solid Tumors
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Agent(s): PF-07265028 and Sasanlimab
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Disease Type(s): Solid Tumor
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Phase(s): I
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Drug Classification(s): Immunotherapy, Small Molecule, Targeted Therapy
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Molecular Target(s): HPK1
Mechanism of Action
PF-07265028 is a hematopoietic progenitor kinase 1 inhibitor. This inhibits Hpk-1-mediated signaling pathways which inhibit the lymphocytes. It also prevents Hpk1-mediated immunosuppression by preventing the inhibition of T-cell receptors (TCR) signaling and effector T cells, disrupting abnormal cytokine expression, and abrogating the immunosuppressive tumor microenvironment (TME).
Sasanlimab targets and binds to PD-1 and blocks the interaction between PD-1 and its ligands, PD-1 ligand 1 (PD-L 1) and PD-1 ligand 2 (PD-L2). This may restore immune function through the activation of natural killer (NK) cells and cvtotoxic T lvmohocvtes (CTLs) aaainst tumor cells.
Purpose
In this study, the sponsor and investigators want to learn:
- How much of PF-07265028 can be given with an acceptable level of side effects alone and in combination with sasanlimab
- The effects of PF-07265028 (good and bad) alone and in combination with sasanlimab
- How much of PF-07265028 is absorbed into the blood and how fast it is removed
Across all cohorts:
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Adequate hematological, kidney and liver function
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Resolved acute effects of any prior therapy
- All participants must provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue:
- Part 1: If archival sample is older than 6 months, the participant must consent to undergo a fresh biopsy during the screening
- Part 2 Fresh tumor biopsy during screening is required unless there is archival tissues less than 3 months old and subsequent to the last systemic anti-cancer therapy
Part 1A Monotherapy:
- Histologically or cytologically confirmed advanced or metastatic solid tumors which have progressed following systemic anticancer therapies, or are resistant to standard therapy or for which no standard therapy is available, or for whom standard therapy is not tolerated
Part 1B Combination Therapy:
- Histologically or cytologically confirmed advanced or metastatic solid tumor which have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor
Part 2 Dose Expansion:
- Histologically or cytologically confirmed advanced or metastatic malignancies, including gastric/Gastroesophageal junction cancer, Head and neck squamous cell carcinoma, or urothelial cancer (non-small cell lung cancer and other solid tumors may be included) who have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor
- Participants with any other active malignancy within 3 years prior to enrollment
- Participants with active autoimmune conditions or history of autoimmune diseases that may relapse
- History of interstitial lung disease, pneumonitis (non-infectious) or uncontrolled lung diseases
- History of prior immune-related adverse events (irAEs) Grade ≥3
- Central nervous system metastases
- Significant cardiac or pulmonary conditions or events within previous 6 months
- Active, uncontrolled bacterial, fungal, or viral infection
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PF-07265028
- Prior administration of HPK1 inhibitor
Location
- Dallas, TX - Mary Crowley Cancer Research - Medical City
