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

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.

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.

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