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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат STK-012
  Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
• Препарат pembrolizumab KEYTRUDA®
  anti-PD-1 monoclonal antibody
• Препарат pemetrexed
  chemotherapy
• Препарат carboplatin
  chemotherapy

Первичные конечные точки

• Phase 1a: Treatment emergent adverse events (TEAEs) [Срок оценки: From 1st dose of study treatment through 90 days after last dose]
• Phase 1a: Serious adverse events (SAEs) [Срок оценки: From 1st dose of study treatment through 90 days after last dose]
• Phase 1a: Dose limiting toxicities (DLTs) [Срок оценки: Cycle 1, Days 1 through 21]
• Phase 1a: Deaths [Срок оценки: From 1st dose of study treatment until death, up to 4 years]
• Phase 1b: TEAEs at the RP2D [Срок оценки: From 1st dose of study treatment through 90 days after last dose]
• Phase 1b: SAEs at the RP2D [Срок оценки: From 1st dose of study treatment through 90 days after last dose]
• Phase 1b: Deaths at the RP2D [Срок оценки: From 1st dose of study treatment until death, up to 4 years]
• Phase 2: Overall response rate (ORR) in Arm A versus Arm C [Срок оценки: From randomization until disease progression or death, or the last evaluable assessment in the absence of progression, up to 4 years]

Вторичные конечные точки (12)

• Phase 1: ORR [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: From enrollment until death due to any cause, up to 4 years]
• Phase 1/2: STK-012 ADAs [Срок оценки: From screening through 30 days after last dose of STK-012]
• Phase 1/2: AUC of STK-012 [Срок оценки: From screening through 30 days after last dose of STK-012]
• Phase 1/2: Cmax of STK-012 [Срок оценки: From screening through 30 days after last dose of STK-012]
• Phase 1/2: Tmax of STK-012 [Срок оценки: From screening through 30 days after last dose of STK-012]
• Phase 1/2: Half life of STK-012 [Срок оценки: From screening through 30 days after last dose of STK-012]
• Phase 2: PFS in Arm A versus Arm C [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From randomization until death due to any cause, up to 4 years]

Критерии участия

Selected Inclusion Criteria:

• Phase 1: Selected advanced solid tumors
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 33 центра

• University of Arizona Cancer Center — Tucson
• Beverly Hills Cancer Center — Beverly Hills
• Providence Medical Foundation — Fullerton
• UC San Diego Moores Cancer Center — La Jolla
• Cedars Sinai — Los Angeles
• Hoag Memorial Hospital Presbyterian — Newport Beach
• UCLA Hematology/Oncology - Santa Monica — Santa Monica
• Yale New Haven Hospital, Yale Cancer Center — New Haven
• … и ещё 25 центров

Испания · 6 центров

• Hospital Quirón Barcelona — Barcelona
• START Rioja — Logroño
• MD Anderson — Madrid
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Regional de Málaga — Málaga
• Clinica Universidad de Navarra - Pamplona — Pamplona

Грузия · 4 центра

• LTD High Technology Hospital Medcenter — Batumi
• Caraps Medline, Ltd (JSC VIAN) — Tbilisi
• Institute of Clinical Oncology (ICO) — Tbilisi
• Israel Georgian Medical Research Clinic Healthycore — Tbilisi

Ирландия · 4 центра

• START Dublin — Dublin
• St. James Hospital — Dublin
• Beaumont Hospital — Dublin
• University Hospital Galway — Galway

Идентификаторы

NCT: NCT05098132 · STK-012-101 · 2025-522632-14-00 · KEYNOTE-G63 · MK-3475-G63

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗