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Advanced Solid TumorPhase 1NCT04691375

A Study of PY314 in Subjects With Advanced Solid Tumors

A Phase 1 study testing PY314 and Combination Therapy: PY314 + Pembrolizumab in people with Advanced Solid Tumor and Gynecologic Cancer, run by Ikena Oncology at 23 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PY314 and Combination Therapy: PY314 + Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
23 sitesUnited States
Study dates
29 Oct 2020to 22 Sep 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 (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.
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  • 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 (including Grade < 2 alopecia or peripheral neuropathy, or if controlled on thyroid replacement therapy).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
  • Coagulation: International Normalized Ratio (INR) ≤ 1.3, unless on a therapeutic anticoagulant
  • Adequate hematologic function defined as follows: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 8.0 g/dL; ANC ≥ 1.5 x 10^9/L (without granulocytic growth factors within the previous 7 days of obtaining the screening hematologic laboratory values)
  • 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
  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Massachusetts General Hospital

    Boston, Massachusetts, 02214

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Chicago

    Chicago, Illinois, 60637

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope - Comprehensive Cancer Center

    Duarte, California, 91010

  • NEXT Virginia

    Fairfax, Virginia, 22031

  • Mayo Clinic Jacksonville - PPDS

    Jacksonville, Florida, 32224

  • Wisconsin Institutes for Medical Research

    Madison, Wisconsin, 53705

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Vanderbilt Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • University of Oklahoma Peggy and Charles Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • Stanford Hospital and Clinics

    Palo Alto, California, 94304

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic Scottsdale - PPDS

    Phoenix, Arizona, 85054

  • OHSU Knight Cancer Institute Beaverton Clinic

    Portland, Oregon, 97239

  • Mayo Clinic - PPDS

    Rochester, Minnesota, 55905

  • Start South Texas Accelerated Research Therapeutics

    San Antonio, Texas, 78229

  • UC San Diego Moores Cancer Center

    San Diego, California, 92093

  • Honor Health Research Institute

    Scottsdale, Arizona, 85258-4566

  • H Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

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

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).

Read the 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

Being tested
PY314, Combination Therapy: PY314 + Pembrolizumab
Medical subject headings
Breast Neoplasms, Colorectal Neoplasms, Adenocarcinoma of Lung, Carcinoma, Renal Cell, Triple Negative Breast Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PY314Drug

    Dose of PY314 as a single agent given in a standard 3+3 design.

  • Combination Therapy: PY314 + PembrolizumabDrug

    Also called PY314, Pembrolizumab

    Dose of PY314 alone and given in combination with pembrolizumab

Study groups in NCT04691375
Study groupRoleWhat they receive
Part A: 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.
Receives: Drug: PY314
Part A: 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.
Receives: Drug: PY314
Part A: 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
Receives: Drug: PY314
Part A: PY314 Single agent dose level 4ExperimentalPY314 single agent dose level 4 to characterize the pharmacokinetic profile of PY314 as a single agent.
Receives: Drug: PY314
Part A: 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.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab
Part A: 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.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab
Part A: Combination dose level 3ExperimentalPY314 combination dose level 3 to characterize the pharmacokinetic profile of PY314 as a single agent and in combination with pembrolizumab.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab
Part A: 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.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab
Part B: Single agent dose expansion dose level 1ExperimentalPY314 single agent dose expansion dose level 1 to define further the safety and tolerability of PY314 alone.
Receives: Drug: PY314
Part B: 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.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab
Part B: 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.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab
Part B: 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.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab
Part B: Combination dose expansion cohort 4ExperimentalPY314 in combination with pembrolizumab dose expansion cohort 4 to evaluate the incidence of ADA formation and TREM2 expression.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab
Part B: Combination dose expansion cohort 5ExperimentalPY314 in combination with pembrolizumab dose expansion cohort 5 to further explore and characterize the anti-tumor activity of PY314 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM2 expression.
Receives: Drug: Combination Therapy: PY314 + Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse Events (AE)

    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.

    Measured: 36 months

  2. (Part A only) Dose Limiting Toxicity of PY314

    Evaluation of dose-limiting toxicity (DLT).

    Measured: Assessed during first 21 days of treatment

Secondary outcomes (12)

  1. Measure PY314 concentration at the end of infusion (CEOI)

    Measure PY314 concentration at the end of infusion (CEOI) after the first dose.

    Measured: 36 months

  2. Measure PY314 concentration at the trough level (Ctrough)

    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.

    Measured: 36 months

  3. Determining PY314 time to maximum concentration (Tmax)

    Determining PY314 time to maximum concentration (Tmax) during Cycle 1.

    Measured: 36 months

  4. Measure PY314 Area under the curve (AUC)0-t

    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.

    Measured: 36 months

  5. Measure PY314 half-life (T1/2)

    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.

    Measured: 36 months

  6. Measure PY314 Clearance (CL)

    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.

    Measured: 36 months

  7. Measure PY314 Volume at Steady State (Vss)

    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.

    Measured: 36 months

  8. Measure PY314 maximum concentration (Cmax)

    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.

    Measured: 36 months

  9. Incidence of Anti-Drug Antibody (ADA) formation to PY314

    To evaluate the incidence of anti-drug antibody (ADA) formation to PY314

    Measured: 36 months

  10. Objective response rate (ORR)

    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.

    Measured: 36 months

  11. Clinical Benefit Rate (CBR)

    Defined as the percentage of subjects who have achieved complete response, partial response and stable disease.

    Measured: 36 Months

  12. Duration of response (DOR)

    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.

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2020
  2. Study start29 Oct 2020
  3. Primary completion31 Aug 2023
  4. Study completion22 Sep 2023

Why it stopped: Sponsor business decision.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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)
Enrolment
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04691375
Sponsor's protocol ID
PY314-1-01
Status last verified
Mar 2024
First submitted
8 Dec 2020
Last updated
22 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Beckermann KE, Patnaik A, Winer I, Tan W, Bashir B, Kyriakopoulos CE, Sweis RF, Chamberlain M, Rini BI. A phase 1b open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of py314 in combination with pembrolizumab in patients with advanced renal cell carcinoma. Invest New Drugs. 2024 Apr;42(2):179-184. doi: 10.1007/s10637-024-01419-1. Epub 2024 Feb 19.

    PubMed 38372949

  • Binnewies M, Pollack JL, Rudolph J, Dash S, Abushawish M, Lee T, Jahchan NS, Canaday P, Lu E, Norng M, Mankikar S, Liu VM, Du X, Chen A, Mehta R, Palmer R, Juric V, Liang L, Baker KP, Reyno L, Krummel MF, Streuli M, Sriram V. Targeting TREM2 on tumor-associated macrophages enhances immunotherapy. Cell Rep. 2021 Oct 19;37(3):109844. doi: 10.1016/j.celrep.2021.109844.

    PubMed 34686340

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PY314 and Combination Therapy: PY314 + Pembrolizumab in people with Advanced Solid Tumor and Gynecologic Cancer, run by Ikena Oncology at 23 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor business decision.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events (AE) (time frame: 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04691375, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024; AzTrials last refreshed its copy on 26 Oct 2026.

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