1st Line NSCLC, Advanced Solid Tumor, Non Small Cell Lung Cancer, Untreated Advanced NSCLC
Conditions
Brief summary
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.
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.
Interventions
DRUGSTK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
anti-PD-1 monoclonal antibody
DRUGpemetrexed
chemotherapy
DRUGcarboplatin
chemotherapy
Sponsors
Synthekine
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Treatment emergent adverse events (TEAEs) | From 1st dose of study treatment through 90 days after last dose | Incidence of TEAEs in participants with select advanced solid tumors |
| Phase 1a: Serious adverse events (SAEs) | From 1st dose of study treatment through 90 days after last dose | Incidence of SAEs in participants with select advanced solid tumors |
| Phase 1a: Dose limiting toxicities (DLTs) | Cycle 1, Days 1 through 21 | Incidence of DLTs in participants with select advanced solid tumors |
| Phase 1a: Deaths | From 1st dose of study treatment until death, up to 4 years | Incidence of death in participants with select advanced solid tumors |
| Phase 1b: TEAEs at the RP2D | 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 |
| Phase 1b: SAEs at the RP2D | 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 |
| Phase 1b: Deaths at the RP2D | 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 |
| Phase 2: Overall response rate (ORR) in Arm A versus Arm C | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: ORR | 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. |
| Phase 1: Progression free survival (PFS) | 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. |
| Phase 1: Overall survival (OS) | From enrollment until death due to any cause, up to 4 years | Assessment of preliminary efficacy, specifically OS, in select advanced solid tumors. |
| Phase 1/2: STK-012 ADAs | 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. |
| Phase 1/2: AUC of STK-012 | 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. |
| Phase 1/2: Cmax of STK-012 | 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. |
| Phase 1/2: Tmax of STK-012 | 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. |
| Phase 1/2: Half life of STK-012 | 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. |
| Phase 2: PFS in Arm A versus Arm C | 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. |
| Phase 2: ORR in Arm B versus Arm C | 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. |
| Phase 2: PFS in Arm B versus Arm C | 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. |
| Phase 2: OS in Arm A versus C | 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. |
| Phase 2: OS in Arm B versus C | 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. |
| Phase 2: TEAEs | From 1st dose of study treatment through 90 days after last dose | Incidence of TEAEs in 1L NSQ NSCLC (PD-L1\<1% or STK11m) |
| Phase 2: SAEs | From 1st dose of study treatment through 90 days after last dose | Incidence of SAEs in 1L NSQ NSCLC (PD-L1\<1% or STK11m) |
| Phase 2: Deaths | From 1st dose of study treatment until death, up to 4 years | Incidence of death in 1L NSQ NSCLC (PD-L1\<1% or STK11m) |
Countries
Georgia, Ireland, Spain, United States
Contacts
CONTACTSynthekine STK-012-101 Contact
Outcome results
None listed