Clinical trial NCT04682431: A Phase 1a/1b FIH Study of PY159 and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Gynecologic Cancer
Breast Cancer
Colorectal Cancer
Gastric Adenocarcinoma
Lung Adenocarcinoma
Pancreatic Cancer
Head and Neck Cancer
Lead sponsor: Ikena Oncology
Sponsor class: INDUSTRY
First posted: 2020-12-23
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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
Primary purpose: TREATMENT

Brief summary: 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).

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

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Adverse Events (AE)
timeFrame: 36 months
measure: Dose Limiting Toxicity of PY159 (Part A only)
timeFrame: 21 days
Secondary outcomes:
measure: Measure PY159 concentration at the end of infusion (CEOI)
timeFrame: 36 months
measure: Measure PY159 maximum concentration (Cmax)
timeFrame: 36 months
measure: Measure PY159 concentration at the trough level (Ctrough)
timeFrame: 36 months
measure: Measure PY159 Area under the curve (AUC)0-t
timeFrame: 36 months
measure: Measure PY159 half-life (T1/2)
timeFrame: 36 months
measure: Measure PY159 Clearance (CL)
timeFrame: 36 months
measure: Measure PY159 Volume at Steady State (Vss)
timeFrame: 36 months
measure: Incidence of Anti-Drug Antibody (ADA) formation to PY159
timeFrame: 36 months
measure: Determining PY159 time to maximum concentration (Tmax)
timeFrame: 36 months
measure: Objective response rate (ORR)
timeFrame: 36 months
measure: Clinical Benefit Rate (CBR)
timeFrame: 36 months
measure: Duration of response (DOR)
timeFrame: 36 months
Other outcomes:
measure: Progress free survival (PFS)
timeFrame: 36 months
measure: Overall survival (OS)
timeFrame: 36 months
Locations:
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Mount Zion Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Parkside Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: Sarasota
country: United States
facility: Florida Cancer Specialists - Sarasota - SCRI
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Norman
country: United States
facility: The University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Start South Texas Accelerated Research Therapeutic
state: Texas
Study officials:
affiliation: Ikena Oncology
name: Len Reyno, MD
role: STUDY_DIRECTOR
affiliation: Ikena Oncology
name: Marc Chamberlain, MD
role: STUDY_DIRECTOR
References: