A Phase 1a/1b FIH Study of PY159 and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

March 20, 2024 updated by: Ikena Oncology

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

This is an open-label, multicenter, First-In-Human (FIH), Phase 1a/1b study of PY159 in subjects with locally advanced (unresectable) and/or metastatic solid tumors that are refractory or relapsed to Standard Of Care (including Checkpoint Inhibitors, if approved for that indication).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Actual)

127

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90089
        • USC Norris Cancer Center
      • San Francisco, California, United States, 94115
        • UCSF Mount Zion Cancer Center
      • Santa Monica, California, United States, 90404
        • UCLA Parkside Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Smilow Cancer Hospital at Yale New Haven
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists - Sarasota - SCRI
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5116
        • Indiana University
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers Cancer Institute of New Jersey
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
    • Oklahoma
      • Norman, Oklahoma, United States, 73019
        • The University of Oklahoma
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Center
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Start South Texas Accelerated Research Therapeutic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 advanced solid tumors from pre-specified tumor types:

    • head and neck [squamous cell carcinoma, salivary gland, thyroid],
    • gynecologic [including ovarian, fallopian, primary peritoneal, endometrial, cervical, uterine, vaginal, vulvar],
    • pancreatic [adenocarcinoma],
    • 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,
    • gastric and esophagogastric junction adenocarcinomas [MSI low and CPI refractory MSI high],
    • breast [TNBC and HR+, HER2-] with 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).
  • Subjects must provide an original, diagnostic tumor sample to determine TREM1 expression (sites have verified source prior to screening and availability of archival tissue during screening). For Part A subjects without an archival tissue sample will only be eligible if they choose and consent to provide a CNB of a primary or metastatic lesion.
  • Subjects must have documented radiographic disease progression that include 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 < 2 before the start of study drug dosing (except for alopecia or peripheral neuropathy which may be Grade <2 or medication controlled thyroid replacement therapy).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.

Exclusion Criteria

  • Subject is a candidate for approved 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 well controlled on replacement therapy.
  • Untreated and/or uncontrolled brain metastases Stable treated or asymptomatic brain metastases (for at least 1 month prior to enrollment may be enrolled. Subjects with stable treated or asymptomatic brain metastases receiving glucocorticoids must be on a stable dose [≤ 2 mg/day of dexamethasone or an equivalent glucocorticoid] for a minimum of 1month 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 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.
  • Any anti-cancer therapy, including small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy (with the exception of bone-modifying agents as supportive care), radiotherapy or any other agents to treat cancer within 14-21 days (dependent upon the agent and drug half-life) 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.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: PY159 Single agent dose level 1
PY159 dose level 1 IV administration, Q3 weekly until consent withdrawal, intolerable toxicity or investigator decision.
Drug: PY159 Single agent dose level 1
Dose of PY159 as a single agent given in a standard 3+3 design.
Other Names:
  • PY159
Experimental: Part A: PY159 Single agent dose level 2
PY159 dose level 2
Drug: PY159 Single agent dose level 2
Dose of PY159 as a single agent given in a standard 3+3 design.
Other Names:
  • PY159
Experimental: Part A: PY159 single agent dose level 3
PY159 dose level 3
Drug: PY159 Single agent dose level 3
Dose of PY159 as a single agent given in a standard 3+3 design.
Other Names:
  • PY159
Experimental: Part A: PY159 single agent dose level 4
PY159 dose level 4
Drug: PY159 Single agent dose level 4
Dose of PY159 as a single agent given in a standard 3+3 design.
Other Names:
  • PY159
Experimental: Part A: PY159 single agent dose level 5
PY159 dose level 5
Drug: PY159 Single agent dose level 5
Dose of PY159 as a single agent given in a standard 3+3 design.
Other Names:
  • PY159
Experimental: Part A: PY159 single agent dose level 6
PY159 dose level 6
Drug: PY159 Single agent dose level 6
Dose of PY159 as a single agent given in a standard 3+3 design.
Other Names:
  • PY159
Experimental: Part A: PY159 single agent dose level 7
PY159 dose level 7
Drug: PY159 Single agent dose level 7
Dose of PY159 as a single agent given in a standard 3+3 design.
Other Names:
  • PY159
Experimental: Part A: PY159/Pembrolizumab Combination dose level 1
PY159 dose level 1 in combination with pembrolizumab
Drug: PY159/Pembrolizumab Combination dose level 1
Dose of PY159 and given in combination with pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159
Experimental: Part A: PY159/Pembrolizumab Combination dose level 2
PY159 dose level 2 in combination with pembrolizumab
Drug: PY159/Pembrolizumab Combination dose level 2
Dose of PY159 and given in combination with pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159
Experimental: Part A: PY159/Pembrolizumab Combination dose level 3
PY159 dose level 3 in combination with pembrolizumab
Drug: PY159/Pembrolizumab Combination dose level 3
Dose of PY159 and given in combination with pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159
Experimental: Part A: PY159/Pembrolizumab Combination dose level 4
PY159 dose level 4 in combination with pembrolizumab
Drug: PY159/Pembrolizumab Combination dose level 4
Dose of PY159 and given in combination with pembrolizumab
Other Names:
  • Pembrolizumab
  • PY159
Experimental: PY159 Part B: Single agent dose expansion cohort(s)
PY159 Single agent dose expansion cohort(s)
Drug: PY159 Single agent dose expansion cohort
Dose of PY159 as a single agent given for predefined tumor histology
Other Names:
  • PY159
Experimental: PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 1
PY159 in combination with pembrolizumab dose expansion cohort 1 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
Drug: PY159/Pembrolizumab Combination dose expansion cohort 1
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Other Names:
  • Pembrolizumab
  • PY159
Experimental: PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 2
PY159 in combination with pembrolizumab dose expansion cohort 2 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
Drug: PY159/Pembrolizumab Combination dose expansion cohort 2
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Other Names:
  • Pembrolizumab
  • PY159
Experimental: PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 3
PY159 in combination with pembrolizumab dose expansion cohort 3 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
Drug: PY159/Pembrolizumab Combination dose expansion cohort 3
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Other Names:
  • Pembrolizumab
  • PY159
Experimental: PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 4
PY159 in combination with pembrolizumab dose expansion cohort 4 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
Drug: PY159/Pembrolizumab Combination dose expansion cohort 4
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Other Names:
  • Pembrolizumab
  • PY159
Experimental: PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 5
PY159 in combination with pembrolizumab dose expansion cohort 5 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
Drug: PY159/Pembrolizumab Combination dose expansion cohort 5
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Other Names:
  • Pembrolizumab
  • PY159
Experimental: PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 6
PY159 in combination with pembrolizumab dose expansion cohort 6 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression.
Drug: PY159/Pembrolizumab Combination dose expansion cohort 6
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Other Names:
  • Pembrolizumab
  • PY159

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events (AE)
Time Frame: 36 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.
36 months
Dose Limiting Toxicity of PY159 (Part A only)
Time Frame: 21 days
Evaluation of dose-limiting toxicity (DLT).
21 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
36 months
Measure PY159 concentration at the end of infusion (CEOI)
Time Frame: 36 months
Measure PY159 concentration at the end of infusion (CEOI) after the first dose.
36 months
Measure PY159 maximum concentration (Cmax)
Time Frame: 36 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 pharmacokinetics (PK) time point after start of dosing.
36 months
Measure PY159 concentration at the trough level (Ctrough)
Time Frame: 36 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.
36 months
Measure PY159 Area under the curve (AUC)0-t
Time Frame: 36 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.
36 months
Measure PY159 half-life (T1/2)
Time Frame: 36 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.
36 months
Measure PY159 Clearance (CL)
Time Frame: 36 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.
36 months
Measure PY159 Volume at Steady State (Vss)
Time Frame: 36 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.
36 months
Incidence of Anti-Drug Antibody (ADA) formation to PY159
Time Frame: 36 months
To evaluate the incidence of anti-drug antibody (ADA) formation to PY159
36 months
Determining PY159 time to maximum concentration (Tmax)
Time Frame: 36 months
Determining PY159 time to maximum concentration (Tmax) during Cycle 1.
36 months
Objective response rate (ORR)
Time Frame: 36 months
The incidents of ORR is defined as either a complete or partial response (PR) 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.
36 months
Clinical Benefit Rate (CBR)
Time Frame: 36 months
Defined as the percentage of subjects who have achieved complete response (CR), partial response (PR) and stable disease (SD).
36 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
36 months
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.
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ikena Oncology

Collaborators

Gilead Sciences

Investigators

  • Study Director: Len Reyno, MD, Ikena Oncology
  • Study Director: Marc Chamberlain, MD, Ikena Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 10, 2020

Primary Completion (Actual)

August 25, 2023

Study Completion (Actual)

August 31, 2023

Study Registration Dates

First Submitted

December 11, 2020

First Submitted That Met QC Criteria

December 22, 2020

First Posted (Actual)

December 23, 2020

Study Record Updates

Last Update Posted (Actual)

March 22, 2024

Last Update Submitted That Met QC Criteria

March 20, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PY159-2-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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