An Open-Label, Multicenter, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of RO7296682 in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 49
- 试验地点
- 10
- 主要终点
- Part 1: Number of Participants With Adverse Events (AEs)
研究概览
简要总结
This study will evaluate the safety, tolerability and preliminary anti-tumor activity of RO7296682 in combination with Atezolizumab in participants with advanced solid tumors.
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
- •Diagnosis of advanced and/or metastatic solid tumors who have progressed on a standard therapy, are intolerant to standard of care (SoC), and/or and non-amenable to SoC.
- •Participants whose tumors have known sensitizing mutations must have experienced disease progression (during or after treatment) or intolerance to treatment with a respective targeted therapy.
- •Measurable disease according to RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Able to provide the most recent archival tumor tissue samples.
- •Adequate cardiovascular, haematological, liver and renal function.
- •Participants on therapeutic anticoagulation must be on a stable anticoagulant regimen.
- •Women of Childbearing Potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods.
- •Men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods and refrain from donating sperm.
排除标准
- •Pregnancy, lactation, or breastfeeding.
- •Known hypersensitivity to any of the components of RO7296682 and atezolizumab, including but not limited to hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
- •History or clinical evidence of central nervous system (CNS) primary tumors or metastases.
- •Participants with another invasive malignancy in the last two years.
- •Participants with known active or uncontrolled infection.
- •Positive HIV test at screening.
- •Positive for Hepatitis B and C.
- •Vaccination with live vaccines within 28 days prior to C1D
- •Major surgical procedure or significant traumatic injury within 28 days prior to first RO7296682 and atezolizumab infusion.
- •Participants with wound healing complications.
- •Dementia or altered mental status that would prohibit informed consent.
- •History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug rash with eosinophilia and systemic symptoms).
- •Active or history of autoimmune disease or immune deficiency.
- •Prior treatment with CPIs (e.g. anti-CTLA4, anti-PD1, anti-PDL1), immunomodulatory monoclonal antibodies (mAbs) and/or mAb-derived therapies (approved or investigational) is approved.
- •Treatment with standard radiotherapy, any chemotherapeutic agent, targeted therapy or treatment with any other investigational drug (defined as treatment for which there is currently no regulatory authority-approved indication) within 28 days or 5 half-lives of the drug (whichever is shorter), prior to the first RO7296882 administration on C1D
- •Radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy (for which no wash out period is required).
研究组 & 干预措施
Part I
Dose-Escalation: Mixed solid tumors participants will receive ascending doses of RO7296682 with a fixed dose of Atezolizumab, every three weeks (Q3W) until either the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is defined.
干预措施: RO7296682 (Drug)
Part I
Dose-Escalation: Mixed solid tumors participants will receive ascending doses of RO7296682 with a fixed dose of Atezolizumab, every three weeks (Q3W) until either the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is defined.
干预措施: Atezolizumab (Drug)
Part II
Dose-Expansion: Will start once MTD/RP2D dose of RO7296682 in combination with Atezolizumab is defined in Part I. Participants with selected tumor types will receive a fixed dose of RO7296682 in combination with Atezolizumab.
干预措施: RO7296682 (Drug)
Part II
Dose-Expansion: Will start once MTD/RP2D dose of RO7296682 in combination with Atezolizumab is defined in Part I. Participants with selected tumor types will receive a fixed dose of RO7296682 in combination with Atezolizumab.
干预措施: Atezolizumab (Drug)
Part III (Exploratory)
Dose-Expansion: Will start once MTD/RP2D dose of RO7296682 in combination with Atezolizumab is defined in Part I and if clinical activity is seen in this trial or in the single agent study (WP41188). Participants with selected tumor types will receive a fixed dose of RO7296682 in combination with Atezolizumab at the dosing regimen established in Part I.
干预措施: RO7296682 (Drug)
Part III (Exploratory)
Dose-Expansion: Will start once MTD/RP2D dose of RO7296682 in combination with Atezolizumab is defined in Part I and if clinical activity is seen in this trial or in the single agent study (WP41188). Participants with selected tumor types will receive a fixed dose of RO7296682 in combination with Atezolizumab at the dosing regimen established in Part I.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Part 1: Number of Participants With Adverse Events (AEs)
时间窗: From Day 1 up to the end of safety follow-up (up to 28.5 months)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of a causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.
Part 2: Number of Participants With AEs
时间窗: From Day 1 up to the end of safety follow-up (up to 9.3 months)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of a causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.
Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: From Cycle 1 Day 1 up Cycle 2 Day 8 (1 Cycle = 21 days)
A DLT was defined as the occurrence of any of the following toxicities related to RO7296682 and atezolizumab that occurs during the DLT assessment window and not attributable to the underlying disease or an intercurrent illness: Any Grade ≥ 3 hematologic toxicity; Any Grade ≥ 3 non-hematologic toxicity; any other RO7296682-related toxicity considered significant enough to qualify as a DLT in the opinion of the Investigator and after discussion with the Sponsor.
Part 2: Objective Response Rate (ORR)
时间窗: Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
ORR was determined as the percentage of participants with an overall response (OR) of complete response (CR) or partial response (PR) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. Percentages have been rounded off to the nearest decimal point.
次要结局
- Part 1: ORR(From Day 1 up to end of safety follow-up (up to 28.5 months))
- Part 1 and 2: Disease Control Rate (DCR)(Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months))
- Part 1 and 2: Duration of Response (DoR)(Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months))
- Part 1 and 2: Progression-Free Survival (PFS)(Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months))
- Part 1 and 2: Overall Survival (OS)(Part 1: From Day 1 up to end of survival follow-up (36 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months))
- Part 1 and 2: Area Under the Curve From Time of Dosing to the Last Timepoint at the End of the Dosing Period (AUClast) of RO7296682(Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days))
- Part 1 and 2: Maximum Concentration (Cmax) of RO7296682(Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days))
- Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682(Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days))
- Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682(Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days))
- Part 1 and 2: Half-life (t~1/2) of RO7296682(Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days))
- Part 1: Serum Concentration of Atezolizumab(Predose on Day 1 of Cycles 1 to 9, 12, 14, and 17; End of infusion (EOI) on Day 1 of Cycles 1 and 4; end of study/early discontinuation (up to 28.5 months))
- Part 1 and 2: Number of Participants With Treatment-induced Changes in T Regulatory C Ells (Treg) Levels in Blood and/or Tumor as Compared to Baseline(Baseline up to 28 days post last dose (up to 24.9 months))
- Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline(Cycle 1 Day 1 (end of infusion [EOI]); Cycle 1 Day 4 (72 hours post dose); Cycle 1 Day 8 (168 hours post dose); Cycle 1 Day 15 (336 hours post dose))