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A Study of PY314 in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04691375
Recruitment Status : Recruiting
First Posted : December 31, 2020
Last Update Posted : December 31, 2020
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Pionyr Immunotherapeutics Inc.

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: Dose of PY314 Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 216 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model 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
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 29, 2020
Estimated Primary Completion Date : October 28, 2022
Estimated Study Completion Date : October 28, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PY314 Single agent dose level 1
PY314 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.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: PY314 Single agent dose level 2
PY314 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.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: PY314 Single agent dose level 3
PY314 single agent dose level 3 to identify the maximum tolerated dose and/or to determine the recommended dose for expansion of PY314
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: PY314 Single agent dose level 4
PY314 single agent dose level 4 to characterize the pharmacokinetic profile of PY314 as a single agent.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Combination dose level 1
Combination 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.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Combination dose level 2
PY314 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.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Combination dose level 3
PY314 combination dose level 3 to characterize the pharmacokinetic profile of PY314 as a single agent and in combination with pembrolizumab.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Combination dose level 4
PY314 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.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Single agent dose expansion dose level 1
PY314 single agent dose expansion dose level 1 to define further the safety and tolerability of PY314 alone.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Single agent dose expansion dose level 2
PY314 single agent dose expansion dose level 2 to further characterize the PK profile of PY314 as a single agent.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Combination dose expansion cohort 1
PY314 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.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Combination dose expansion cohort 2
PY314 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.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Combination dose expansion cohort 3
PY314 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.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab

Experimental: Combination dose expansion cohort 4
PY314 in combination with pembrolizumab dose expansion cohort 4 to evaluate the incidence of ADA formation and TREM2 expression.
Drug: Dose of PY314
Dose of PY314 alone and given in combination with pembrolizumab in a standard 3+3 design.
Other Name: Pembrolizumab




Primary Outcome Measures :
  1. Incidence of Adverse Events (AE) [ Time Frame: 12 months ]
    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.

  2. Measure PY314 concentration at the end of infusion (CEOI) [ Time Frame: 12 months ]
    Measure PY314 concentration at the end of infusion (CEOI) after the first dose.

  3. Measure PY314 maximum concentration (Cmax) [ Time Frame: 12 months ]
    Measure PY314 maximum concentration (Cmax) at various time points during Cycle 1. All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.

  4. Measure PY314 concentration at the trough level (Ctrough) [ Time Frame: 12 months ]
    Measure PY314 concentration at the trough level (Ctrough). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.

  5. Determining PY314 time to maximum concentration (Tmax) [ Time Frame: 12 months ]
    Determining PY314 time to maximum concentration (Tmax) during Cycle 1.

  6. Measure PY314 Area under the curve (AUC)0-t [ Time Frame: 12 months ]
    Measure PY314 Area under the curve (AUC)0-t. All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.

  7. Measure PY314 half-life (T1/2) [ Time Frame: 12 months ]
    Measure PY314 half-life (T1/2). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.

  8. Measure PY314 Clearance (CL) [ Time Frame: 12 months ]
    Measure PY314 Clearance (CL). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.

  9. Measure PY314 Volume at Steady State (Vss) [ Time Frame: 12 months ]
    Measure PY314 Volume at Steady State (Vss). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.

  10. Incidence of Anti-Drug Antibody (ADA) formation to PY314 [ Time Frame: 12 months ]
    To evaluate the incidence of anti-drug antibody (ADA) formation to PY314


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 36 months ]
    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.

  2. Deceased control rate (DCR) [ Time Frame: 36 months ]
    DCR will be measure per resists 1.1 criteria. DCR will be summarized descriptively.

  3. Duration of response (DOR) [ Time Frame: 36 months ]
    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.

  4. Progress free survival (PFS) [ Time Frame: 36 months ]
    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.

  5. Overall survival (OS) [ Time Frame: 36 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04691375


Contacts
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Contact: Len Reyno, MD 310-498-6960 lreyno@pionrytx.com
Contact: Akin Akinsola 217-637-1792 aakinsola@pionrytx.com

Locations
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United States, Arizona
Honor Health Research Institute Not yet recruiting
Scottsdale, Arizona, United States, 85258-4566
Contact: Paul McKinney    480-323-3805    paul.mckinney@honorhealth.com   
Mayo Clinic Scottsdale - PPDS Not yet recruiting
Scottsdale, Arizona, United States, 85259
Contact: Katie Gano    480-342-6082    gano.katherine@mayo.edu   
United States, Colorado
University of Colorado Hospital Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Mark Morrow    720-848-0665    mark.morrow@cuanschutz.edu   
United States, Florida
Mayo Clinic Jacksonville - PPDS Not yet recruiting
Jacksonville, Florida, United States, 32224
Contact: Katie Gano    480-342-6082    gano.katherine@mayo.edu   
United States, Michigan
Karmanos Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Clarice Zuccaro    313-576-9375    zuccaroc@karmanos.org   
United States, Minnesota
Mayo Clinic - PPDS Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Katie Gano    480-342-6082    gano.katherine@mayo.edu   
United States, Tennessee
Sarah Cannon Research Institute, LLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: Rachel De Jesus    615-320-5090    Rachel.DeJesus@SarahCannon.com   
United States, Texas
Start South Texas Accelerated Research Therapeutic Recruiting
San Antonio, Texas, United States, 78229
Contact: Jasmine DeBlanc    210-593-5978    jasmine.deblanc@startsa.com   
Sponsors and Collaborators
Pionyr Immunotherapeutics Inc.
Gilead Sciences
Investigators
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Study Director: Lynnae Jackson Pionyr Immunotherapuetics, Inc.
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Responsible Party: Pionyr Immunotherapeutics Inc.
ClinicalTrials.gov Identifier: NCT04691375    
Other Study ID Numbers: PY314-1-01
First Posted: December 31, 2020    Key Record Dates
Last Update Posted: December 31, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents