Advanced Solid Tumor, Non Small Cell Lung Cancer, Untreated Advanced NSCLC, 1st Line 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, non-squamous, non-small cell lung cancer.
Detailed description
Phase 1 \[closed to enrollment\]: 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 \[open to enrollment\]: 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, non-squamous, non-small cell lung cancer.
Interventions
DRUGSTK-012
Engineered Interleukin-2 (IL-2) selective for antigen activated T cells
DRUGpembrolizumab
anti-PD-1 monoclonal antibody
DRUGpemetrexed
chemotherapy
DRUGcarboplatin
chemotherapy
Sponsors
Synthekine
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 \[closed to enrollment\] 2. Phase 2 \[open to enrollment\]: * 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. * Tumor is PD-L1 negative (TPS \<1%) by local testing. * 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
1. Phase 1 \[closed to enrollment\] 2. Phase 2 \[open to enrollment\]: * Prior immune checkpoint inhibitor (anti-PD\[L\]1 and/or anti-CTLA-4) treatment * Tumor with small cell, neuroendocrine, or sarcomatoid components. * Received radiotherapy ≤ 7 days of the first dose of study treatment. * Known untreated 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 PD-L1 negative NSQ NSCLC 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 PD-L1 negative NSQ NSCLC 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 PD-L1 negative NSQ NSCLC 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 PD-L1 negative NSQ NSCLC 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 PD-L1 negative NSQ NSCLC 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 PD-L1 negative NSQ NSCLC 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 PD-L1 negative NSQ NSCLC |
| Phase 2: SAEs | From 1st dose of study treatment through 90 days after last dose | Incidence of SAEs in 1L PD-L1 negative NSQ NSCLC |
| Phase 2: Deaths | From 1st dose of study treatment until death, up to 4 years | Incidence of death in 1L PD-L1 negative NSQ NSCLC |
Countries
United States
Contacts
CONTACTSynthekine STK-012-101 Contact
Outcome results
None listed