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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 364
- 试验地点
- 60
- 主要终点
- Phase 1a: Treatment emergent adverse events (TEAEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Selected Inclusion Criteria:
- •Phase 1: Selected advanced solid tumors
- •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.
排除标准
- •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
研究组 & 干预措施
Phase 2: Arm A
STK-012 2.25 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: pemetrexed (Drug)
Phase 2: Arm C
SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: pemetrexed (Drug)
Phase 2: Arm B
STK-012 1.5 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: pembrolizumab KEYTRUDA® (Drug)
Phase 1a: STK-012 + pembrolizumab dose escalation
STK-012 SC + pembrolizumab intravenously (IV) in selected solid tumor indications
干预措施: pembrolizumab KEYTRUDA® (Drug)
Phase 1b: STK-012 + SoC dose expansion
STK-012 SC + SoC IV in first-line PD-L1 negative NSQ NSCLC
干预措施: pembrolizumab KEYTRUDA® (Drug)
Phase 1a: STK-012 + standard of care (SoC) dose escalation
STK-012 SC + SoC IV in first-line non-squamous (NSQ) NSCLC
干预措施: carboplatin (Drug)
Phase 1b: STK-012 monotherapy expansion
STK-012 SC monotherapy in selected solid tumor indications
干预措施: STK-012 (Drug)
Phase 1b: STK-012 + SoC dose expansion
STK-012 SC + SoC IV in first-line PD-L1 negative NSQ NSCLC
干预措施: carboplatin (Drug)
Phase 1b: STK-012 + pembrolizumab dose expansion
STK-012 SC will be administered in combination with pembrolizumab IV in selected solid tumor indications
干预措施: pembrolizumab KEYTRUDA® (Drug)
Phase 2: Arm B
STK-012 1.5 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: carboplatin (Drug)
Phase 1a: STK-012 monotherapy dose escalation
STK-012 subcutaneous (SC) as monotherapy in selected solid tumor indications
干预措施: STK-012 (Drug)
Phase 2: Arm B
STK-012 1.5 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: pemetrexed (Drug)
Phase 1a: STK-012 + standard of care (SoC) dose escalation
STK-012 SC + SoC IV in first-line non-squamous (NSQ) NSCLC
干预措施: STK-012 (Drug)
Phase 2: Arm C
SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: pembrolizumab KEYTRUDA® (Drug)
Phase 2: Arm B
STK-012 1.5 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: STK-012 (Drug)
Phase 2: Arm C
SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: carboplatin (Drug)
Phase 1b: STK-012 + pembrolizumab dose expansion
STK-012 SC will be administered in combination with pembrolizumab IV in selected solid tumor indications
干预措施: STK-012 (Drug)
Phase 1a: STK-012 + standard of care (SoC) dose escalation
STK-012 SC + SoC IV in first-line non-squamous (NSQ) NSCLC
干预措施: pemetrexed (Drug)
Phase 1b: STK-012 + SoC dose expansion
STK-012 SC + SoC IV in first-line PD-L1 negative NSQ NSCLC
干预措施: pemetrexed (Drug)
Phase 1b: STK-012 + SoC dose expansion
STK-012 SC + SoC IV in first-line PD-L1 negative NSQ NSCLC
干预措施: STK-012 (Drug)
Phase 1a: STK-012 + pembrolizumab dose escalation
STK-012 SC + pembrolizumab intravenously (IV) in selected solid tumor indications
干预措施: STK-012 (Drug)
Phase 2: Arm A
STK-012 2.25 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: pembrolizumab KEYTRUDA® (Drug)
Phase 2: Arm A
STK-012 2.25 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: STK-012 (Drug)
Phase 1a: STK-012 + standard of care (SoC) dose escalation
STK-012 SC + SoC IV in first-line non-squamous (NSQ) NSCLC
干预措施: pembrolizumab KEYTRUDA® (Drug)
Phase 2: Arm A
STK-012 2.25 mg SC Q3W + SoC IV in first-line PD-L1 negative or STK11 mutated, NSQ NSCLC
干预措施: carboplatin (Drug)
结局指标
主要结局
Phase 1a: Treatment emergent adverse events (TEAEs)
时间窗: 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)
时间窗: 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)
时间窗: Cycle 1, Days 1 through 21
Incidence of DLTs in participants with select advanced solid tumors
Phase 1a: Deaths
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
Phase 1a: Treatment emergent adverse events (TEAEs)
时间窗: 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)
时间窗: 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)
时间窗: Cycle 1, Days 1 through 21
Incidence of DLTs in participants with select advanced solid tumors
Phase 1a: Deaths
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Phase 1: ORR(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)(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)(From enrollment until death due to any cause, up to 4 years)
- Phase 1/2: STK-012 ADAs(From screening through 30 days after last dose of STK-012)
- Phase 1/2: AUC of STK-012(From screening through 30 days after last dose of STK-012)
- Phase 1/2: Cmax of STK-012(From screening through 30 days after last dose of STK-012)
- Phase 1/2: Tmax of STK-012(From screening through 30 days after last dose of STK-012)
- Phase 1/2: Half life of STK-012(From screening through 30 days after last dose of STK-012)
- 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)
- 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)
- 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)
- Phase 2: OS in Arm A versus C(From randomization until death due to any cause, up to 4 years)
- Phase 2: Deaths(From 1st dose of study treatment until death, up to 4 years)
- 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)
- Phase 2: Deaths(From 1st dose of study treatment until death, up to 4 years)
- Phase 2: OS in Arm B versus C(From randomization until death due to any cause, up to 4 years)
- Phase 2: TEAEs(From 1st dose of study treatment through 90 days after last dose)
- Phase 2: SAEs(From 1st dose of study treatment through 90 days after last dose)
- Phase 1: ORR(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)(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)(From enrollment until death due to any cause, up to 4 years)
- Phase 1/2: STK-012 ADAs(From screening through 30 days after last dose of STK-012)
- Phase 1/2: AUC of STK-012(From screening through 30 days after last dose of STK-012)
- Phase 1/2: Cmax of STK-012(From screening through 30 days after last dose of STK-012)
- Phase 1/2: Tmax of STK-012(From screening through 30 days after last dose of STK-012)
- Phase 1/2: Half life of STK-012(From screening through 30 days after last dose of STK-012)
- 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)
- 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)
- Phase 2: OS in Arm A versus C(From randomization until death due to any cause, up to 4 years)