A Phase 1, Open-Label, Multicenter Study of INCA33890 in Participants With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 570
- 试验地点
- 75
- 主要终点
- Dose Limiting Toxicities (DLTs)
研究概览
简要总结
To evaluate the safety, tolerability, and DLTs and determine the MTD and/or RDE(s) of INCA33890 in participants with select advanced or metastatic 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
- •≥18 years old
- •Histologically or cytologically confirmed advanced or metastatic malignancies as defined in the protocol.
- •Part 1: Participants must have experienced disease progression after treatment with, be intolerant to, or be ineligible for, or refused available therapies, including anti-PD-(L)1 or anti-CTLA4 therapy if applicable, that are known to confer clinical benefit. Part 2: depending on cohort, participants may have received or not prior treatment for the malignancy under study.
- •ECOG performance status score of 0 or
- •Willingness to undergo pre- and on-treatment tumor biopsy (core or excisional). Biopsies are mandatory depending on the cohorts.
- •Presence of measurable disease according to RECIST v1.1.
排除标准
- •Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years.
- •Not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy.
- •Has active autoimmune disease requiring systemic immunosuppression with corticosteroids.
- •Brain or CNS metastases untreated or that have progressed.
- •History of organ transplant, including allogeneic stem cell transplantation.
- •History of clinically significant or uncontrolled cardiac disease.
- •Active HBV, active HCV, or HIV positive.
- •Is on chronic systemic steroids (> 10 mg/day of prednisone or equivalent).
- •Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
- •Participants that have been initiated on or had modifications in anticoagulation therapies within the last 3 months prior to first dose of treatment.
- •Significant concurrent, uncontrolled medical condition, eg:
- •Cardiovascular: Participants with known vasculitis, aneurisms, and other vascular malformations of clinical significance or history of myocarditis.
- •Gastrointestinal: Any bowel obstruction within 60 days prior to C1D
- •Participants with adequate laboratory values within the protocol defined ranges.
- •Other protocol-defined Inclusion/Exclusion Criteria may apply.
研究组 & 干预措施
Part 2a - Dose Escalation Combination Therapy - Group 2
INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment.
干预措施: FOLFIRI (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 2
INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment.
干预措施: FOLFIRI (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 3
INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment.
干预措施: FOLFOX (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 4
INCA33890 will be administered in combination with cetuximab at the protocol-defined dose based on cohort assignment.
干预措施: Cetuximab (Drug)
Part 1a - Dose Escalation Monotherapy
INCA33890 will be administered at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 5
INCA33890 will be administered in combination with ADG126 at the protocol-defined dose based on cohort assignment.
干预措施: ADG126 (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 3
INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 3
INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment.
干预措施: bevacizumab (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 4
INCA33890 will be administered in combination with cetuximab at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 5
INCA33890 will be administered in combination with ADG126 at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 5
INCA33890 will be administered in combination with ADG126 at the protocol-defined dose based on cohort assignment.
干预措施: ADG126 (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 3
INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment.
干预措施: FOLFOX (Drug)
Part 1b-Dose Expansion Monotherapy
INCA33890 will be administered at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 1
INCA33890 will be administered in combination with bevacizumab at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 1
INCA33890 will be administered in combination with bevacizumab at the protocol-defined dose based on cohort assignment.
干预措施: bevacizumab (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 2
INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 2
INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment.
干预措施: bevacizumab (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 3
INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 3
INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment.
干预措施: bevacizumab (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 4
INCA33890 will be administered in combination with cetuximab at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2a - Dose Escalation Combination Therapy - Group 4
INCA33890 will be administered in combination with cetuximab at the protocol-defined dose based on cohort assignment.
干预措施: Cetuximab (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 1
INCA33890 will be administered in combination with bevacizumab at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 1
INCA33890 will be administered in combination with bevacizumab at the protocol-defined dose based on cohort assignment.
干预措施: bevacizumab (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 2
INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 2
INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment.
干预措施: bevacizumab (Drug)
Part 2b - Dose Expansion Combination Therapy - Group 5
INCA33890 will be administered in combination with ADG126 at the protocol-defined dose based on cohort assignment.
干预措施: INCA33890 (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLTs)
时间窗: Up to 28 days
Treatment Emerging Adverse Events (TEAEs)
时间窗: Up to 2 years
TEAEs leading to dose modification or discontinuation
时间窗: Up to 2 years
次要结局
- Objective response Rate(2 years)
- Disease Control Rate(2 years)
- Duration of Response(2 years)
- Pharmacokinetics Parameter : Cmax of INCA33890(Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up)
- Pharmacokinetics Parameter : AUC(0-t) of INCA33890(Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up)
- Pharmacokinetics Parameter : AUC 0-∞ of INCA33890(Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up)
- Pharmacokinetics Parameter : Tmax of INCA33890(Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up)
- Pharmacokinetics Parameter : Cmin of INCA33890(Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up)
- Pharmacokinetics Parameter : CL of INCA33890(Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up)
- Pharmacokinetics Parameter : Vz of INCA33890(Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up)
- Pharmacokinetics Parameter : t1/2 of INCA33890(Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up)