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A Phase 1a/1b First-In-Human (FIH) Study of PY159 in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04682431
Recruitment Status : Recruiting
First Posted : December 23, 2020
Last Update Posted : December 23, 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 PY159 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: PY159 Single agent dose level 1 Drug: PY159 Single agent dose level 2 Drug: PY159 Single agent dose level 3 Drug: PY159 Single agent dose level 4 Drug: PY159 Single agent dose level 5 Drug: PY159 Single agent dose level 6 Drug: PY159 Single agent dose level 7 Drug: PY159/Pembrolizumab Combination dose level 1 Drug: PY159/Pembrolizumab Combination dose level 2 Drug: PY159/Pembrolizumab Combination dose level 3 Drug: PY159/Pembrolizumab Combination dose level 4 Drug: PY159 Single agent dose expansion cohort 1 Drug: PY159 Single agent dose expansion cohort 2 Drug: PY159/Pembrolizumab Combination dose expansion cohort 1 Drug: PY159/Pembrolizumab Combination dose expansion cohort 2 Drug: PY159/Pembrolizumab Combination dose expansion cohort 3 Drug: PY159/Pembrolizumab Combination dose expansion cohort 4 Phase 1

Detailed Description:
Part A: Dose escalation of PY159 alone and in combination with pembrolizumab n a standard 3+3 design Part B: Dose expansion of one or more dose levels of PY159 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 PY159 alone and in combination with pembrolizumab in a standard 3+3 design Part B: Dose expansion of one or more dose levels of PY159 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 PY159 as a Single Agent and In Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
Actual Study Start Date : November 10, 2020
Estimated Primary Completion Date : November 9, 2023
Estimated Study Completion Date : November 9, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PY159 Single agent dose level 1
PY159 single agent dose level 1 IV administration, Q3 weekly until consent withdrawal, intolerable toxicity or investigator decision.
Drug: PY159 Single agent dose level 1
PY159 experimental drug

Experimental: PY159 Single agent dose level 2
PY159 single agent dose level 2
Drug: PY159 Single agent dose level 2
PY159 experimental drug

Experimental: PY159 single agent dose level 3
PY159 single agent dose level 3
Drug: PY159 Single agent dose level 3
PY159 experimental drug

Experimental: PY159 single agent dose level 4
PY159 single agent dose level 4
Drug: PY159 Single agent dose level 4
PY159 experimental drug

Experimental: PY159 single agent dose level 5
PY159 single agent dose level 5
Drug: PY159 Single agent dose level 5
PY159 experimental drug

Experimental: PY159 single agent dose level 6
PY159 single agent dose level 6
Drug: PY159 Single agent dose level 6
PY159 experimental drug

Experimental: PY159 single agent dose level 7
PY159 single agent dose level 7
Drug: PY159 Single agent dose level 7
PY159 experimental drug

Experimental: PY159/Pembrolizumab Combination dose level 1
PY159/Pembrolizumab Combination dose level 1
Drug: PY159/Pembrolizumab Combination dose level 1
Combination PY159 & Pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159

Experimental: PY159/Pembrolizumab Combination dose level 2
PY159/Pembrolizumab Combination dose level 2
Drug: PY159/Pembrolizumab Combination dose level 2
Combination PY159 & Pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159

Experimental: PY159/Pembrolizumab Combination dose level 3
PY159/Pembrolizumab Combination dose level 3
Drug: PY159/Pembrolizumab Combination dose level 3
Combination PY159 & Pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159

Experimental: PY159/Pembrolizumab Combination dose level 4
PY159/Pembrolizumab Combination dose level 4
Drug: PY159/Pembrolizumab Combination dose level 4
Combination PY159 & Pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159

Experimental: PY159 Single agent dose expansion cohort 1
PY159 Single agent dose expansion cohort 1
Drug: PY159 Single agent dose expansion cohort 1
PY159 experimental drug

Experimental: PY159 Single agent dose expansion cohort 2
PY159 Single agent dose expansion cohort 2
Drug: PY159 Single agent dose expansion cohort 2
PY159 experimental drug

Experimental: PY159/Pembrolizumab Combination dose expansion cohort 1
PY159 in combination with pembrolizumab dose expansion cohort 1
Drug: PY159/Pembrolizumab Combination dose expansion cohort 1
Combination PY159 & Pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159

Experimental: PY159/Pembrolizumab Combination dose expansion cohort 2
PY159 in combination with pembrolizumab dose expansion cohort 2
Drug: PY159/Pembrolizumab Combination dose expansion cohort 2
Combination PY159 & Pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159

Experimental: PY159/Pembrolizumab Combination dose expansion cohort 3
PY159 in combination with pembrolizumab dose expansion cohort 3
Drug: PY159/Pembrolizumab Combination dose expansion cohort 3
Combination PY159 & Pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159

Experimental: PY159/Pembrolizumab Combination dose expansion cohort 4
PY159 in combination with pembrolizumab dose expansion cohort 4
Drug: PY159/Pembrolizumab Combination dose expansion cohort 4
Combination PY159 & Pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159




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 PY159 concentration at the end of infusion (CEOI) [ Time Frame: 12 months ]
    Measure PY159 concentration at the end of infusion (CEOI) after the first dose.

  3. Measure PY159 maximum concentration (Cmax) [ Time Frame: 12 months ]
    Measure PY159 maximum concentration (Cmax) at various time points during Cycle 1. All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.

  4. Measure PY159 concentration at the trough level (Ctrough) [ Time Frame: 12 months ]
    Measure PY159 concentration at the trough level (Ctrough). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.

  5. Determining PY159 time to maximum concentration (Tmax) [ Time Frame: 12 months ]
    Determining PY159 time to maximum concentration (Tmax) during Cycle 1.

  6. Measure PY159 Area under the curve (AUC)0-t [ Time Frame: 12 months ]
    Measure PY159 Area under the curve (AUC)0-t. All subjects who received at least 1 dose of PY159 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 PY159 half-life (T1/2) [ Time Frame: 12 months ]
    Measure PY159 half-life (T1/2). All subjects who received at least 1 dose of PY159 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 PY159 Clearance (CL) [ Time Frame: 12 months ]
    Measure PY159 Clearance (CL). All subjects who received at least 1 dose of PY159 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 PY159 Volume at Steady State (Vss) [ Time Frame: 12 months ]
    Measure PY159 Volume at Steady State (Vss). All subjects who received at least 1 dose of PY159 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 PY159 [ Time Frame: 12 months ]
    To evaluate the incidence of anti-drug antibody (ADA) formation to PY159


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 (head and neck cancer, gynecological cancers [including ovarian, endometrial, cervix, vagina, vulva], pancreatic [adenocarcinoma], lung [adenocarcinoma and squamous cell carcinoma], gastric [adenocarcinoma MSIlow and CPI refractory MSIhigh ], breast [Triple Negative Breast Cancer (TNBC) and Hormone Receptor Positive Breast Cancer (HR+), HER-2 negative Breast Cancer (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 Programmed Cell Death-1 (PD-1)/Programmed Cell Death-Ligand 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 TREM1 expression confirmed by IHC (of fresh CNB) prior to enrollment. 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.
  3. Subjects must provide an original, diagnostic tumor sample to determine TREM1 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 (e.g. thyroid replacement therapy) before the start of study drug dosing, except for alopecia, peripheral neuropathy, or hypothyroidism
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2

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. Untreated or uncontrolled brain metastases. (Treated, stable and asymptomatic metastases for at least 3 months prior to enrollment may be enrolled). Stable subjects with brain metastases receiving glucocorticoids must be on a stable dose for at least 3 months prior to enrollment.
  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 Congestive Heart Failure (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, 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. Subjects with a prior history of prostate cancer on LHRH agonist are eligible provided they have no evidence of metastatic disease.

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): NCT04682431


Contacts
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Contact: Len Reyno, MD 310-498-6960 lreyno@pionrytx.com
Contact: Lynnae Jackson 805-750-0553 ljackson@pionrytx.com

Locations
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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: NCT04682431    
Other Study ID Numbers: PY159-2-01
First Posted: December 23, 2020    Key Record Dates
Last Update Posted: December 23, 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