A Study of PY314 in Subjects With Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2023-10-28
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, multicenter, first in human, Phase 1a/1b study of PY314 in subjects with locally advanced (unresectable) and/or metastatic solid tumors that are refractory or relapsed to standard of care (including pembrolizumab, if approved for that indication).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pionyr Immunotherapeutics Inc.
• Collaborator: Gilead Sciences
• Treatments: Pembrolizumab

Criteria

KEY ELIGIBILITY CRITERIA

Inclusion Criteria:

• Adults ≥18 years of age at the time of study consent

• Subjects with any of the following eligible solid tumor diagnoses as confirmed by cytology or histology:

• Escalation Cohorts (Part A): Subjects with solid tumors from pre-specified tumor types (gynecological cancers [including ovarian, endometrial, cervix, vagina, vulva], gastric [adenocarcinoma], colon [MSIlow],(MSIlow and CPI refractory MSIhigh) ], Colon (MSIlow and CPI refractory MSIhigh), lung [adenocarcinoma], renal [clear cell and non-clear cell], breast [TNBC and HR+ HER-2-] with metastatic disease that is relapsed or refractory to at least one line of metastatic therapy (including a CPI-either alone or in combination- if approved for that indication, and not eligible for other targeted therapies specific for their tumor type). Lung adenocarcinoma subjects who are relapsed or refractory to platinum-based chemotherapy in addition to prior treatment with PD-1/PD-L1 or who give informed consent to forego such therapy.

• Expansion Cohorts (Part B): Subjects with advanced solid tumors selected from prespecified histologic subgroups identified in Part A.

• Subjects must provide an original, diagnostic tumor sample to determine TREM2 expression (Investigators have verified source and availability of archival tissue during screening). Subjects without an archival tissue sample will only be eligible if they choose and consent to provide a CNB of primary or a metastatic lesion required for part B, used in Part A only if an archival specimen unavailable.

• Subjects must have documented disease progression (Part A, including prior treatment with a CPI (alone or in combination), if approved for that indication

• Measurable disease by RECIST 1.1

• All acute toxic effects of any prior antitumor therapy, including immunotherapy, resolved to Grade ≤ 1 or < 2 if controlled on medications (eg thyroid replacement therapy) before the start of study drug dosing

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2

• Coagulation: International Normalized Ratio (INR) ≤ 1.3, unless on a therapeutic anticoagulant

• Adequate hematologic function defined as follows: Platelets ≥ 100 x 109/L; Hemoglobin ≥ 9.0 g/dL; ANC ≥ 1.5 x 109/L (without any granulocytic growth factors within previous 7 days of the screening hematologic laboratory values)

• Adequate hepatic function defined as follows: AST / ALT ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN

• Adequate renal function defined as follows: Serum Creatinine ≤ 2 x ULN or creatinine clearance (CrCl) ≥45 mL/min as calculated by the Cockroft-Gault method

Exclusion Criteria:

• Patient is a candidate for molecularly targeted therapy (e.g. drugs targeting EGFR, EGFR, ALK, ROS-1, NTRK, MET, RET and BRAF V600E, Her2neu)). Applies to enrolled subjects on both Part A and Part B of the study.

• History of autoimmune disorder requiring ongoing or intermittent disease-modifying therapy

• Stable treated or asymptomatic brain metastases for at least 3 months documented by brain imaging prior to enrollment

• Uncontrolled intercurrent illness including, but not limited to, active or chronic bleeding event within 28 days prior to first dose of study drug, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician

• Decompensated liver disease as evidenced by hepatic encephalopathy or coagulopathy

• Active angina or Class III or IV CHF (NYHA CHF Functional Classification System) or clinically significant cardiac disease within 12 months of first dose of study drug, including MI, unstable angina, Grade 2 or greater peripheral vascular disease, CHF, uncontrolled HTN, or arrhythmias not controlled by medication

• Any anti-cancer therapy, including small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy, or any other agents to treat cancer within 14 days, of first dose of study drug

• Part B: excluding refractory lung cancer subjects who have progressed within 3 months of initiating chemotherapy-doublet regimens or lung cancer subjects who have progressed within 6 months of initiation immunotherapy-chemotherapy combination treatment

Note: Other protocol defined Inclusion/Exclusion criteria may apply.