Study of STK-012 Alone and With Other Treatments in Patients With Advanced Lung Cancer and Other Cancers (SYNERGY-101)

July 17, 2026 updated by: Synthekine

A Phase 1/2 Study to Evaluate STK-012 as a Single Agent and in Combination Therapy in Subjects With Front-line Advanced NSCLC and Other Selected Indications

This is a phase 1/2, multicenter, open-label study. The phase 1 portion is a dose escalation and expansion study of STK-012 as monotherapy and in combination therapy in patients with selected advanced solid tumors. The phase 2 portion is a randomized study of STK-012 in combination with standard of care (SoC) pembrolizumab, pemetrexed, and carboplatin versus SoC, in patients with first line, PD-L1 negative or STK11 mutated, non-squamous, non-small cell lung cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Phase 1: The phase 1a portion is a dose escalation study to evaluate STK-012 as monotherapy and in combination therapy in patients with selected solid tumors. The phase 1b portion is a dose expansion study to evaluate STK-012 as monotherapy and in combination therapy at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types.

Phase 2: The phase 2 portion is a randomized, open label study to evaluate STK-012 at two dose levels in combination with standard of care (SoC) pembrolizumab, pemetrexed and carboplatin, versus SoC, in patients with first line, PD-L1 negative or STK11 mutated, non-squamous, non-small cell lung cancer. Subjects in the randomized Phase 2 portion (Part G) will be randomized 1:1:1 and stratified by tumor PD-L1 expression and STK11 mutation status.

Study Type

Interventional

Enrollment (Estimated)

364

Phase

  • Phase 2
  • 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 Locations

  • Georgia
      • Batumi, Georgia, 6000
        • Recruiting
        • LTD High Technology Hospital Medcenter
      • Tbilisi, Georgia, 0159
        • Recruiting
        • Caraps Medline, Ltd (JSC VIAN)
      • Tbilisi, Georgia, 0159
        • Recruiting
        • Institute of Clinical Oncology (ICO)
      • Tbilisi, Georgia, 0159
        • Recruiting
        • Israel Georgian Medical Research Clinic Healthycore
  • Ireland
      • Dublin, Ireland, 07
        • Recruiting
        • START Dublin
      • Dublin, Ireland, 08
        • Recruiting
        • St. James Hospital
      • Dublin, Ireland, 09
        • Recruiting
        • Beaumont Hospital
      • Galway, Ireland, H91 YR71
        • Recruiting
        • University Hospital Galway
  • Spain
      • Barcelona, Spain, 08023
        • Recruiting
        • Hospital Quiron Barcelona
      • Logroño, Spain, 26006
        • Recruiting
        • START Rioja
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon Y Cajal
      • Madrid, Spain, 28033
        • Recruiting
        • MD Anderson
      • Málaga, Spain, 29011
        • Recruiting
        • Hospital Regional de Malaga
      • Pamplona, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra - Pamplona
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85721
    • California
      • Beverly Hills, California, United States, 90211
      • Fullerton, California, United States, 92835
      • La Jolla, California, United States, 92093-0698
        • Active, not recruiting
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars Sinai
      • Newport Beach, California, United States, 92663
      • Santa Monica, California, United States, 90404
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale New Haven Hospital, Yale Cancer Center
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20057
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Winship Cancer Institute, Emory University
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University Of Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
      • Boston, Massachusetts, United States, 02215
      • Boston, Massachusetts, United States, 02215
    • Minnesota
      • Saint Paul, Minnesota, United States, 55101
    • New York
      • Lake Success, New York, United States, 11042
      • New York, New York, United States, 10016
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan-Kettering Cancer Center
        • Contact:
      • New York, New York, United States, 10032
        • Active, not recruiting
        • Columbia University Irving Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Active, not recruiting
        • Duke Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The James Cancer Hospital and Solove Research Institute
        • Contact:
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97123
        • Recruiting
        • Providence Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • Terminated
        • UPMC Hillman Cancer Center
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • Active, not recruiting
        • Baptist Memorial Hospital Cancer Center
      • Nashville, Tennessee, United States, 37203
        • Active, not recruiting
        • Sarah Cannon Research Institute - Nashville
    • Texas
      • El Paso, Texas, United States, 79915
        • Withdrawn
        • Renovatio Clinical
      • Houston, Texas, United States, 77303
      • The Woodlands, Texas, United States, 77380
        • Withdrawn
        • Renovatio Clinical
    • Virginia
      • Fairfax, Virginia, United States, 22031
    • Washington
      • Tacoma, Washington, United States, 98405
        • Active, not recruiting
        • Northwest Medical Specialties

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

Selected Inclusion Criteria:

  1. Phase 1: Selected advanced solid tumors

  2. Phase 2:

    • Diagnosis of non-small cell lung cancer (NSCLC).
    • Stage IV or Stage IIIB/IIIC and not a candidate for definitive treatment.
    • Non-squamous (NSQ) cell histology.
    • No prior systemic therapy for advanced/metastatic NSQ NSCLC.

    • Must have a tumor that meets at least one of the following criteria on local testing:

      • PD-L1 negative (TPS <1%), OR;
      • STK11 mutated on tumor tissue or ctDNA
    • No known actionable EGFR, ALK, ROS1, or other actionable genomic aberrations for which there is a local standard of care available as front line therapy.

Selected Exclusion Criteria:

2. Phase 2:

  • Prior immune checkpoint inhibitor (anti-PD[L]1 and/or anti-CTLA-4) treatment
  • Rare tumor subtypes (mucinous histology or tumors with small cell, neuroendocrine, or sarcomatoid components).
  • Received radiotherapy ≤ 7 days of the first dose of study treatment.
  • Known active central nervous system metastases
  • Any history of carcinomatous meningitis

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1a: STK-012 monotherapy dose escalation
STK-012 subcutaneous (SC) as monotherapy in selected solid tumor indications
Drug: STK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
Experimental: Phase 1a: STK-012 + pembrolizumab dose escalation
STK-012 SC + pembrolizumab intravenously (IV) in selected solid tumor indications
Drug: STK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
Drug: pembrolizumab KEYTRUDA®
anti-PD-1 monoclonal antibody
Experimental: Phase 1a: STK-012 + standard of care (SoC) dose escalation
STK-012 SC + SoC IV in first-line non-squamous (NSQ) NSCLC
Drug: carboplatin
chemotherapy
Drug: STK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
Drug: pemetrexed
chemotherapy
Drug: pembrolizumab KEYTRUDA®
anti-PD-1 monoclonal antibody
Experimental: Phase 1b: STK-012 monotherapy expansion
STK-012 SC monotherapy in selected solid tumor indications
Drug: STK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
Experimental: Phase 1b: STK-012 + pembrolizumab dose expansion
STK-012 SC will be administered in combination with pembrolizumab IV in selected solid tumor indications
Drug: STK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
Drug: pembrolizumab KEYTRUDA®
anti-PD-1 monoclonal antibody
Experimental: Phase 1b: STK-012 + SoC dose expansion
STK-012 SC + SoC IV in first-line PD-L1 negative NSQ NSCLC
Drug: carboplatin
chemotherapy
Drug: STK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
Drug: pemetrexed
chemotherapy
Drug: pembrolizumab KEYTRUDA®
anti-PD-1 monoclonal antibody
Experimental: Phase 2: Arm A
STK-012 2.25 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
Drug: carboplatin
chemotherapy
Drug: STK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
Drug: pemetrexed
chemotherapy
Drug: pembrolizumab KEYTRUDA®
anti-PD-1 monoclonal antibody
Experimental: Phase 2: Arm B
STK-012 1.5 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
Drug: carboplatin
chemotherapy
Drug: STK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
Drug: pemetrexed
chemotherapy
Drug: pembrolizumab KEYTRUDA®
anti-PD-1 monoclonal antibody
Active Comparator: Phase 2: Arm C
SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
Drug: carboplatin
chemotherapy
Drug: pemetrexed
chemotherapy
Drug: pembrolizumab KEYTRUDA®
anti-PD-1 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1a: Treatment emergent adverse events (TEAEs)
Time Frame: From 1st dose of study treatment through 90 days after last dose
Incidence of TEAEs in participants with select advanced solid tumors
From 1st dose of study treatment through 90 days after last dose
Phase 1a: Serious adverse events (SAEs)
Time Frame: From 1st dose of study treatment through 90 days after last dose
Incidence of SAEs in participants with select advanced solid tumors
From 1st dose of study treatment through 90 days after last dose
Phase 1a: Dose limiting toxicities (DLTs)
Time Frame: Cycle 1, Days 1 through 21
Incidence of DLTs in participants with select advanced solid tumors
Cycle 1, Days 1 through 21
Phase 1a: Deaths
Time Frame: From 1st dose of study treatment until death, up to 4 years
Incidence of death in participants with select advanced solid tumors
From 1st dose of study treatment until death, up to 4 years
Phase 1b: TEAEs at the RP2D
Time Frame: From 1st dose of study treatment through 90 days after last dose
Incidence of TEAEs at the recommended phase 2 dose (RP2D) in participants with select advanced solid tumors
From 1st dose of study treatment through 90 days after last dose
Phase 1b: SAEs at the RP2D
Time Frame: From 1st dose of study treatment through 90 days after last dose
Incidence of SAEs at the RP2D in participants with select advanced solid tumors
From 1st dose of study treatment through 90 days after last dose
Phase 1b: Deaths at the RP2D
Time Frame: From 1st dose of study treatment until death, up to 4 years
Incidence of death at the RP2D in participants with select advanced solid tumors
From 1st dose of study treatment until death, up to 4 years
Phase 2: Overall response rate (ORR) in Arm A versus Arm C
Time Frame: From randomization until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years
To compare the ORR in 1L NSQ NSCLC (PD-L1<1% or STK11m) subjects treated with STK-012 2.25 mg + SoC vs. SoC (Arms A vs. C). ORR is the proportion of subjects with confirmed complete response (CR) or confirmed partial response (PR) per BICR.
From randomization until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: ORR
Time Frame: From enrollment until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years
Assessment of preliminary efficacy, specifically ORR, in select advanced solid tumors. ORR is the proportion of subjects with confirmed CR or confirmed PR per investigator assessment.
From enrollment until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years
Phase 1: Progression free survival (PFS)
Time Frame: From enrollment until first documentation of disease progression per investigator assessment or death due to any cause, whichever occurs first, up to 4 years
Assessment of preliminary efficacy, specifically PFS, in select advanced solid tumors.
From enrollment until first documentation of disease progression per investigator assessment or death due to any cause, whichever occurs first, up to 4 years
Phase 1: Overall survival (OS)
Time Frame: From enrollment until death due to any cause, up to 4 years
Assessment of preliminary efficacy, specifically OS, in select advanced solid tumors.
From enrollment until death due to any cause, up to 4 years
Phase 1/2: STK-012 ADAs
Time Frame: From screening through 30 days after last dose of STK-012
Anti-drug antibodies (ADA) to assess immunogenicity of STK-012 in advanced NSCLC and other select solid tumors.
From screening through 30 days after last dose of STK-012
Phase 1/2: AUC of STK-012
Time Frame: From screening through 30 days after last dose of STK-012
Area under the curve (AUC) to assess pharmacokinetic (PK) characterization of STK-012 in advanced NSCLC and other select solid tumors.
From screening through 30 days after last dose of STK-012
Phase 1/2: Cmax of STK-012
Time Frame: From screening through 30 days after last dose of STK-012
Maximum concentration (Cmax) to assess PK characterization of STK-012 in advanced NSCLC and other select solid tumors.
From screening through 30 days after last dose of STK-012
Phase 1/2: Tmax of STK-012
Time Frame: From screening through 30 days after last dose of STK-012
Time of maximum concentration (Tmax) to assess PK characterization of STK-012 in advanced NSCLC and other select solid tumors.
From screening through 30 days after last dose of STK-012
Phase 1/2: Half life of STK-012
Time Frame: From screening through 30 days after last dose of STK-012
Half life (t1/2) to assess PK characterization of STK-012 in advanced NSCLC and other select solid tumors.
From screening through 30 days after last dose of STK-012
Phase 2: PFS in Arm A versus Arm C
Time Frame: From randomization until first documentation of disease progression per BICR or death due to any cause, whichever occurs first, up to 4 years
To compare the PFS in 1L NSQ NSCLC (PD-L1<1% or STK11m) subjects treated with STK-012 2.25 mg + SoC vs. SoC (Arms A vs. C). PFS is the time from randomization until the first documentation of disease progression per BICR or death due to any cause, whichever occurs first.
From randomization until first documentation of disease progression per BICR or death due to any cause, whichever occurs first, up to 4 years
Phase 2: ORR in Arm B versus Arm C
Time Frame: From randomization until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years
To compare the ORR in 1L NSQ NSCLC (PD-L1<1% or STK11m) subjects treated with STK-012 1.5 mg + SoC vs. SoC (Arms B vs. C). ORR is the proportion of subjects with confirmed CR or confirmed PR per BICR.
From randomization until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years
Phase 2: PFS in Arm B versus Arm C
Time Frame: From randomization until first documentation of disease progression per BICR or death due to any cause, whichever occurs first, up to 4 years
To compare the PFS in 1L NSQ NSCLC (PD-L1<1% or STK11m) subjects treated with STK-012 1.5 mg + SoC vs. SoC (Arms B vs. C). PFS is the time from randomization until the first documentation of disease progression per BICR or death due to any cause, whichever occurs first.
From randomization until first documentation of disease progression per BICR or death due to any cause, whichever occurs first, up to 4 years
Phase 2: OS in Arm A versus C
Time Frame: From randomization until death due to any cause, up to 4 years
To compare the OS in 1L NSQ NSCLC (PD-L1<1% or STK11m) subjects treated with STK-012 2.25 mg + SoC vs. SoC (Arms A vs. C). OS is the time from randomization until death due to any cause.
From randomization until death due to any cause, up to 4 years
Phase 2: OS in Arm B versus C
Time Frame: From randomization until death due to any cause, up to 4 years
To compare the OS in 1L NSQ NSCLC (PD-L1<1% or STK11m) subjects treated with STK-012 1.5 mg + SoC vs. SoC (Arms B vs. C). OS is the time from randomization until death due to any cause.
From randomization until death due to any cause, up to 4 years
Phase 2: TEAEs
Time Frame: From 1st dose of study treatment through 90 days after last dose
Incidence of TEAEs in 1L NSQ NSCLC (PD-L1<1% or STK11m)
From 1st dose of study treatment through 90 days after last dose
Phase 2: SAEs
Time Frame: From 1st dose of study treatment through 90 days after last dose
Incidence of SAEs in 1L NSQ NSCLC (PD-L1<1% or STK11m)
From 1st dose of study treatment through 90 days after last dose
Phase 2: Deaths
Time Frame: From 1st dose of study treatment until death, up to 4 years
Incidence of death in 1L NSQ NSCLC (PD-L1<1% or STK11m)
From 1st dose of study treatment until death, up to 4 years

Collaborators and Investigators

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

Sponsor

Synthekine

Collaborators

Merck Sharp & Dohme LLC

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)

January 25, 2022

Primary Completion (Estimated)

January 1, 2029

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

October 6, 2021

First Submitted That Met QC Criteria

October 20, 2021

First Posted (Actual)

October 28, 2021

Study Record Updates

Last Update Posted (Actual)

July 21, 2026

Last Update Submitted That Met QC Criteria

July 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STK-012-101
  • 2025-522632-14-00 (Ctis)
  • KEYNOTE-G63 (Other Identifier: Merck Sharp & Dohme LLC)
  • MK-3475-G63 (Other Identifier: Merck Sharp & Dohme LLC)

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

product manufactured in and exported from the U.S.

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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