A Phase 1a/1b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PY314 as a Single Agent and In Combination with Pembrolizumab in Subjects with Advanced Solid Tumors
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).
Part A Dose Escalation (Phase 1a), Primary:
* To characterize the safety and tolerability of PY314 as a single agent and in combination with pembrolizumab in subjects with advanced refractory solid tumors including refractory to CPI if approved for that indication
* To identify the maximum tolerated dose (MTD) and/or to determine the recommended dose for expansion (RDE) of PY314 administered alone and in combination with pembrolizumab for Part B
Part B Dose Expansion (Phase 1b), Primary
* To further define the safety and tolerability of PY314 alone and in combination with pembrolizumab over multiple treatment cycles in subjects with pre-defined tumor histologies
Subjects with any of the following eligible solid tumor diagnoses as confirmed by cytology or histology: Escalation Cohorts (Part A): Subjects with advanced solid tumors from pre-specified tumor types (Gynecological cancers [including ovarian, fallopian, primary peritoneal, endometrial, cervical, vaginal, vulvar], gastric [adenocarcinoma], Colorectal ([MSIlow and CPI refractory MSIhigh]), lung [non-small cell lung adenocarcinoma and squamous cell carcinoma] who are recurrent or refractory to platinum-based chemotherapy in addition to prior treatment with CPI Programmed Cell Death-1 (PD-1)/Programmed Cell Death-Ligand 1 (PD-L1) or who give informed consent to forego such therapy, renal [clear cell and non-clear cell], breast [TNBC and HR+ HER-2-] with locally advanced or metastatic disease that is relapsed or refractory to at least one line of post-adjuvant 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). Expansion Cohorts (Part B): Subjects with advanced solid tumors selected from 5 prespecified cancers based on preclinical and Part A.
Subjects must provide an original, diagnostic tumor sample to determine TREM2 expression (sites have verified source prior to screening 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 (including prior treatment with a CPI (alone or in combination), if approved for that indication.
There is no limit to the number of prior treatments.
Measurable disease by RECIST 1.1
All acute toxic effects of any prior antitumor therapy, including immunotherapy, have resolved to Grade > ECOG Performance Status > Coagulation: International Normalized Ratio (INR) > Adequate organ function defined per protocol
Subject is a candidate for molecularly targeted therapy (e.g., drugs targeting EGFR, VEGF, ALK, ROS-1, NTRK, MET, RET and BRAF V600E, HER2). 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 excluding thyroid disease otherwise well controlled on replacement 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 SARS-CoV-2 infection, 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 (except for bone-modifying agents as supportive care), radiotherapy, or any other agents to treat cancer within 21 days (dependent upon the agent and drug half-life), of first dose of study drug
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.
Please call 1-888-663-3488 for support from a Moffitt representative. New Patients and Healthcare Professionals can submit an online form by selecting the appropriate button below. Existing patients can call 1-888-663-3488. Click here for a current list of insurances accepted at Moffitt.
NEW PATIENTS To request a new patient appointment, please fill out the online form or call 1-888-663-3488.
REFERRING PHYSICIANS Providers and medical staff can refer patients by submitting our online referral form.
Moffit now offers Virtual Visits for patients. If you are eligible for a virtual appointment, our scheduling team will discuss this option further with you.
Moffitt Cancer Center is committed to the health and safety of our patients and their families. For more information on how we’re protecting our new and existing patients, visit our COVID-19 Info Hub