A Multicentric Phase 1/2 Trial to Evaluate the Safety and Efficacy of SOT102 as Monotherapy and in Combination With Standard of Care Treatment in Patients With Gastric and Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 31
- 试验地点
- 8
- 主要终点
- Parts A and B: The Definition of the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of SOT102 Given as Monotherapy and in Combination With First-line SoC Treatment
研究概览
简要总结
This trial will assess the MTD and RP2D of SOT102 administered as monotherapy (Part A) and in combination with first-line SoC treatment (nab-paclitaxel/ gemcitabine; Part B) and efficacy of SOT102 administered as monotherapy (Part C) and in combination with first-line SoC treatment (Part D) in patients with advanced or metastatic pancreatic adenocarcinoma.
详细描述
The trial will have the following parts:
- Part A: Dose escalation, first-in-human, single-agent phase 1 trial of SOT102 in advanced/metastatic pancreatic cancer patients with unmet medical need (CLDN18.2 agnostic)
- Part B : Phase 1b dose escalation combination trial of SOT102 in combination with nab-paclitaxel/gemcitabine as SoC regimen for first-line treatment of patients with advanced/metastatic pancreatic cancer (CLDN18.2 agnostic)
Once an RP2D in the respective phase 1 evaluation (Part A and Part B) has been identified, expansion parts (Part C and Part D) are planned:
- Part C : Single-agent SOT102 expansion at RP2D identified in Part A in pancreatic cancer after one or more prior systemic therapies (second+ line) for locally advanced or metastatic disease (CLDN18.2 positive)
- Part D : SOT102 in combination with nab- paclitaxel/gemcitabine for first-line treatment expansion at RP2D identified in Part B in pancreatic cancer (CLDN18.2 positive)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •All Parts (key criteria)
- •Hematologic: Absolute neutrophil count ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥9 g/dL
- •Hepatic: Bilirubin ≤1.5× upper limits of normal (ULN), ALT and AST ≤2.5×ULN; in case of liver involvement: AST and ALT ≤5×ULN
- •Renal: Creatinine clearance ≥60 mL/min calculated by Cockcroft-Gault formula
- •Prothrombin time/international normalized ratio (INR) ≤1.5×ULN
- •Albumin ≥3.0 mg/dL
- •Proteinuria <1 g/24 hours
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Estimated life expectancy ≥3 months as per investigator's assessment
- •A female patient is eligible to participate if she is not pregnant, not breastfeeding, not of childbearing potential/ agreed with contraception
- •Patient has advanced inoperable or metastatic disease
- •Patient has no better treatment option available
- •Measurable or non-measurable disease according to RECIST 1.1
- •Histological or cytological evidence of adenocarcinoma of pancreas that is advanced or metastatic
- •Part B (in addition to relevant A criteria)*Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic (pancreas)
- •Part C (in addition to relevant A criteria)*Must have received at least one prior systemic therapy for advanced or metastatic disease (pancreas)
- •Part D (in addition to relevant B criteria)*Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced inoperable or metastatic (pancreas)
排除标准
- •All Parts (key criteria)
- •Patient has received radiation therapy ≤14 days before day 1 of cycle 1 or has not recovered to grade ≤1 from treatment-related side effects
- •Severe preexisting medical conditions as per judgement of the investigator (e.g., active gastric or GEJ ulcer with or without bleeding, complete or incomplete gastric outlet syndrome with persistent or repetitive bleeding)
- •History of interstitial pneumonitis or pulmonary fibrosis
- •Symptomatic central nervous system malignancy. Patients with asymptomatic or treated central nervous system metastases may be eligible if they are not treated with corticosteroids or anticonvulsants and the disease is stable for at least 60 days.
- •Patient has peripheral sensory neuropathy grade ≥2
- •Active infection requiring systemic therapy within ≤7 days prior to day 1 of cycle 1
- •History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de Pointes)
- •Bradycardia (<50 beats per minute)
- •Family history of sudden cardiac death before age 50
- •History or family history of congenital long QT syndrome
- •Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing after surgical intervention
- •Time since last transfusion of RBCs ≤14 days before cycle 1 day 1
- •Vaccination with a live or live-attenuated vaccine within 30 days prior the first dose of trial interventions
- •Part B/D (key)
- •*Patients with contraindications to any component of the first-line SoC treatment
研究组 & 干预措施
SOT102 as Monotherapy (Part A) DL1 0.032 mg/kg
Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.032 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes.
干预措施: SOT102 (Drug)
SOT102 as Monotherapy (Part A) DL2 0.064 mg/kg
Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.064 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes.
干预措施: SOT102 (Drug)
SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg
Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.128 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes.
干预措施: SOT102 (Drug)
SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg
Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.214 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes.
干预措施: SOT102 (Drug)
SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg
Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.,32 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes. Upon completion of the SOT102 infusion, first-line SoC treatment was administered. SoC treatment was nab-paclitaxel (125 mg/m2) given as a 30- to 40-minute infusion followed by gemcitabine (1000 mg/m2) given as a 30-minute infusion on days 1, 8, and 15. This treatment was repeated every 28 days.
干预措施: SOT102 (Drug)
结局指标
主要结局
Parts A and B: The Definition of the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of SOT102 Given as Monotherapy and in Combination With First-line SoC Treatment
时间窗: Through Cycles 1-2 (28 days)
MTD is defined as the highest dose level tested below the dose level associated with ≥33% of dose-limiting toxicity (DLT)-evaluable patients experiencing a DLT. The RP2D will be selected based on evaluation of the totality of all data. The trial was halted early due to safety signals not initially deemed DLTs that were seen across different dose levels. After a protocol amendment formally defined this signal as a DLT, the trial was restarted, but the same safety signal reappeared. Following a review by the independent Dose Escalation Committee, the trial was terminated.
Parts C and D: The Assessment of the Efficacy of SOT102 in Monotherapy and in Combination With First-line SoC Treatment
时间窗: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, to be assessed up to approximately 4 years
Efficacy is determined by objective response rate (ORR) determined according to RECIST 1.1 criteria
次要结局
- Parts A and B (Monotherapy and Combination With SoC): Number of Participants With DLTs(Through Cycles 1-2 (28 days))
- Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Treatment-emergent AEs (TEAEs)(Day 1 up to approximately 2 years and 8.5 months)
- Parts A and B (Monotherapy and Combination With SoC): Number of Participants With SOT102-related AEs(Day 1 up to approximately 2 years and 8.5 months)
- Part B (Combination With SoC): Number of Participants With SoC-related AEs(Day 1 up to approximately 2 years and 8.5 months)
- Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Serious AEs (SAEs)(Day 1 up to approximately 2 years and 8.5 months)
- Parts A and B (Monotherapy and Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SOT102(Day 1 up to approximately 2 years and 8.5 months)
- Part B (Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SoC(Day 1 up to approximately 2 years and 8.5 months)
- Parts A and B (Monotherapy and Combination With SoC): Number of Participants Who Died(Day 1 up to approximately 2 years and 8.5 months)
- Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Clinical Laboratory Test Abnormalities (Coagulation, Hematology, Clinical Chemistry and Urinalysis) of Grade 3 or Higher Graded According to NCI CTCAE Version 5.0(Day 1 up to approximately 2 years and 8.5 months)
- Parts A and B (Monotherapy and Combination With SoC): Characterization of Cmax of SOT102(From Day 1 of Cycle 1 until Day 1 of Cycle 5)
- Parts A and B (Monotherapy and Combination With SoC): Characterization of Tmax of SOT102(From Day 1 of Cycle 1 until Day 1 of Cycle 5)
- Parts A and B (Monotherapy and Combination With SoC): Characterization of AUClast of SOT102(From Day 1 of Cycle 1 until Day 1 of Cycle 5)
- Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Complete Response(From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months)
- Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Partial Response(From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months)
- Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Stable Disease(From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months)
- Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Progressive Disease(From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months)
- Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Antibodies Against SOT102(From Day 1 of Cycle 1 until 30 (+5) days after the last dose of SOT102, assessed up to approximately 2 years and 9 months)