Clinical Trials /

A Study of PY314 in Subjects With Advanced Solid Tumors

NCT04691375

Description:

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

Related Conditions:
  • Breast Carcinoma
  • Colon Carcinoma
  • Gastric Adenocarcinoma
  • Lung Adenocarcinoma
  • Malignant Female Reproductive System Neoplasm
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of PY314 in Subjects With Advanced Solid Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: PY314-1-01
  • NCT ID: NCT04691375

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
Dose of PY314PembrolizumabCombination dose expansion cohort 1

Purpose

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

Detailed Description

      Part A: Dose escalation of PY314 alone and in combination with pembrolizumab in a standard
      3+3 design Part B: Dose expansion of one or more dose levels of PY314 administered alone and
      in combination with pembrolizumab for predefined tumor histology
    

Trial Arms

NameTypeDescriptionInterventions
PY314 Single agent dose level 1ExperimentalPY314 single agent dose level will depend on any safety signal observed in this cohorts only. Following the determination of the safety and tolerability of at least two PY314 dose levels by the safety review committee.
  • Dose of PY314
PY314 Single agent dose level 2ExperimentalPY314 single agent dose level 2 dose escalation of PY314 as a single agent will continue in the absence of unacceptable dose limiting toxicity to the maximum administered dose as defined in the predefined dose escalation schema.
  • Dose of PY314
PY314 Single agent dose level 3ExperimentalPY314 single agent dose level 3 to identify the maximum tolerated dose and/or to determine the recommended dose for expansion of PY314
  • Dose of PY314
PY314 Single agent dose level 4ExperimentalPY314 single agent dose level 4 to characterize the pharmacokinetic profile of PY314 as a single agent.
  • Dose of PY314
Combination dose level 1ExperimentalCombination dose level 1 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 check point inhibitor.
  • Dose of PY314
Combination dose level 2ExperimentalPY314 combination dose level 2 to identify the maximum tolerated dose and/or to determine the recommended dose for expansion of PY314 administered alone and in combination with pembrolizumab.
  • Dose of PY314
Combination dose level 3ExperimentalPY314 combination dose level 3 to characterize the pharmacokinetic profile of PY314 as a single agent and in combination with pembrolizumab.
  • Dose of PY314
Combination dose level 4ExperimentalPY314 combination dose level 4 to describe, in subjects selected by pre-specified tumor histology, anti-tumor activity of PY314 administered alone and in combination with pembrolizumab.
  • Dose of PY314
Single agent dose expansion dose level 1ExperimentalPY314 single agent dose expansion dose level 1 to define further the safety and tolerability of PY314 alone.
  • Dose of PY314
Single agent dose expansion dose level 2ExperimentalPY314 single agent dose expansion dose level 2 to further characterize the PK profile of PY314 as a single agent.
  • Dose of PY314
Combination dose expansion cohort 1ExperimentalPY314 in combination with pembrolizumab dose expansion cohort 1 to define the safety and tolerability of PY314 alone and in combination with pembrolizumab over multiple treatment cycles in subjects with pre-defined tumor histologies and confirmed TREM2 expression.
  • Dose of PY314
Combination dose expansion cohort 2ExperimentalPY314 in combination with pembrolizumab dose expansion cohort 2 to further characterize the PK profile of PY314 as a single agent and in combination with pembrolizumab.
  • Dose of PY314
Combination dose expansion cohort 3ExperimentalPY314 in combination with pembrolizumab dose expansion cohort 3 to characterize the anti-tumor activity of PY314 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM2 expression.
  • Dose of PY314
Combination dose expansion cohort 4ExperimentalPY314 in combination with pembrolizumab dose expansion cohort 4 to evaluate the incidence of ADA formation and TREM2 expression.
  • Dose of PY314

Eligibility Criteria

        KEY ELIGIBILITY CRITERIA

        Inclusion Criteria:

          1. Adults ≥18 years of age at the time of study consent

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

               1. 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.

               2. Expansion Cohorts (Part B): Subjects with advanced solid tumors selected from
                  prespecified histologic subgroups identified in Part A, with TREM2 expression
                  confirmed by IHC (of fresh CNB) prior to enrollment. Lung cancer subjects who are
                  relapsed or refractory to prior treatment with an anti- PD-1/PD-L1 antibody and
                  platinum-based chemotherapy or who give informed consent to forego such therapy.

          3. 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 core needle biopsy of a metastatic lesion.

          4. Subjects must have documented disease progression

               1. Part A, including prior treatment with a CPI (alone or in combination), if
                  approved for that indication

               2. Part B, excluding refractory lung cancer patients 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

          5. Measurable disease by RECIST 1.1

          6. 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

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

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

          9. 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)

         10. 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

         11. 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:

          1. 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.

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

          3. Known brain metastases for Part A only. (Treated, stable and asymptomatic metastases
             for at least 3 months prior to enrollment may be enrolled in Part B only)

          4. 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

          5. Decompensated liver disease as evidenced by hepatic encephalopathy or coagulopathy

          6. 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

          7. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events (AE)
Time Frame:12 months
Safety Issue:
Description:Adverse Events will be summarized by MedDRA system organ class and preferred term. Separate tabulations will be produced for all treatment emergent AEs, treatment related AEs, Serious Adverse Events (SAEs), discontinuations due to AEs, and AEs of at least NCI CTCAE grade 3 severity.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:36 months
Safety Issue:
Description:The incidents of ORR is defined as either a complete or partial response per RECIST. Subjects with no baseline data will be considered no responders. ORR will be summarized by dose, tumor type, and overall. ORR will be summarized descriptively.
Measure:Deceased control rate (DCR)
Time Frame:36 months
Safety Issue:
Description:DCR will be measure per resists 1.1 criteria. DCR will be summarized descriptively.
Measure:Duration of response (DOR)
Time Frame:36 months
Safety Issue:
Description:DOR will be calculated to determine durability. DOR will be measured from the time by which the criteria for CR or PR-whichever is recorded first-are met until the first date by which recurrent or progressive disease is objectively documented. DOR will be assessed using KAPLAN-MEIER methods.
Measure:Progress free survival (PFS)
Time Frame:36 months
Safety Issue:
Description:PFS will be measure from entry onto the study until disease progression or death from any cause. PFS will be assessed using KAPLAN-MEIER methods.
Measure:Overall survival (OS)
Time Frame:36 months
Safety Issue:
Description:The duration of overall survival (OS) will be measured from the time of first study drug administration until the date of death. OS will be assessed using KAPLAN-MEIER methods.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pionyr Immunotherapeutics Inc.

Last Updated

December 31, 2020