A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 383
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, pharmacokinetic (PK), pharmacodynamics, and immunogenicity of durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in adult participants with selected advanced solid tumors and the combination of durvalumab and monalizumab (IPH2201) standard of care systemic therapy with or without biological agent and monalizumab (IPH2201) with biological agent administered to participants with recurrent or metastatic colorectal cancer (CRC).
详细描述
The study consists of 3 parts: dose escalation (Part 1), dose expansion (Part 2), and dose exploration (Part 3). Part 1 will evaluate dose escalation of durvalumab in combination with monalizumab in adult participants with select advanced solid tumor malignancies. Part 2 will evaluate further the identified dose of durvalumab in combination with monalizumab from Part 1 in adult participants with select advanced solid tumor malignancies. Part 3 will evaluate dose exploration of durvalumab in combination with monalizumab and standard of care systemic therapy with or without biological agent, and monalizumab in combination with biological agent in adult participants with CRC.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologic documentation of advanced recurrent or metastatic cancer.
- •Participants must be at the recurrent/metastatic setting, with selected advanced solid tumors.
- •Participants must have at least one lesion that is measurable by RECIST v1.1
- •Part 3, Dose exploration, CRC participants can be treatment naïve but should not have received more than two line of systemic therapy in the recurrent/metastatic setting.
- •Exclusion Criteria
- •Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may be permitted upon discussion with the medical monitor.
- •Prior participation in clinical studies that include durvalumab alone or in combination, where the study has registrational intent and the analyses for the primary endpoint have not yet been completed
- •Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment
- •Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.
排除标准
- 未提供
研究组 & 干预措施
Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W
Participants will receive intravenous (IV) infusions of durvalumab 1500 mg every 4 weeks (Q4W) in combination with monalizumab 22.5 mg every 2 weeks (Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed disease progression (PD), or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W
Participants will receive intravenous (IV) infusions of durvalumab 1500 mg every 4 weeks (Q4W) in combination with monalizumab 22.5 mg every 2 weeks (Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed disease progression (PD), or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W
Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 75 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W
Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 75 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W
Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 225 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W
Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 225 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W
Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W
Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W
Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W
Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC)
Participants with microsatellite-stable colorectal cancer (MSS-CRC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC)
Participants with microsatellite-stable colorectal cancer (MSS-CRC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian)
Participants with ovarian cancer will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian)
Participants with ovarian cancer will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS)
Participants with endometrial MSS will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS)
Participants with endometrial MSS will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC)
Participants with non-small cell lung cancer (NSCLC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC)
Participants with non-small cell lung cancer (NSCLC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W
Participants with first-line (1L) MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m^2 IV infusion, folinic acid 400 mg/m^2 infusion, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W
Participants with first-line (1L) MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m^2 IV infusion, folinic acid 400 mg/m^2 infusion, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W
Participants with first-line (1L) MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m^2 IV infusion, folinic acid 400 mg/m^2 infusion, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: mFOLFOX6 (Drug)
Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W
Participants with first-line (1L) MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m^2 IV infusion, folinic acid 400 mg/m^2 infusion, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Bevacizumab (Drug)
Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W
Participants with 1L MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m^2, folinic acid 400 mg/m^2, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (loading dose of 400 mg/m^2 on Day 1, followed by maintenance dose of 250 mg/m^2 IV infusion every week starting on Day 8, then changed to 500 mg/m^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W
Participants with 1L MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m^2, folinic acid 400 mg/m^2, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (loading dose of 400 mg/m^2 on Day 1, followed by maintenance dose of 250 mg/m^2 IV infusion every week starting on Day 8, then changed to 500 mg/m^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W
Participants with 1L MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m^2, folinic acid 400 mg/m^2, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (loading dose of 400 mg/m^2 on Day 1, followed by maintenance dose of 250 mg/m^2 IV infusion every week starting on Day 8, then changed to 500 mg/m^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Cetuximab (Drug)
Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W
Participants with 1L MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m^2, folinic acid 400 mg/m^2, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (loading dose of 400 mg/m^2 on Day 1, followed by maintenance dose of 250 mg/m^2 IV infusion every week starting on Day 8, then changed to 500 mg/m^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: mFOLFOX6 (Drug)
Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W
Participants with recurrent or metastatic third-line (3L) RAS mutant MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W
Participants with recurrent or metastatic third-line (3L) RAS mutant MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W
Participants with recurrent or metastatic third-line (3L) RAS mutant MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Cetuximab (Drug)
Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W
Participants with recurrent or metastatic 3L RAS mutant MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W
Participants with recurrent or metastatic 3L RAS mutant MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Cetuximab (Drug)
Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W
Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W
Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Durvalumab (Drug)
Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W
Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Cetuximab (Drug)
Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W
Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Monalizumab (Drug)
Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W
Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason.
干预措施: Cetuximab (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: Day 1 through 246.9 weeks (maximum observed duration)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. Any TEAEs data is inclusive of both serious and other adverse events (non-serious).
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
时间窗: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in SBP and DBP (minimum post baseline change \[PBC\] and maximum PBC) are reported.
Change From Baseline in Respiratory Rate (RR)
时间窗: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in RR (minimum PBC and maximum PBC) are reported.
Change From Baseline in Pulse Rate (PR)
时间窗: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in PR (minimum PBC and maximum PBC) are reported.
Change From Baseline in Oxygen Saturation (OS)
时间窗: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in OS (minimum PBC and maximum PBC) are reported.
Change From Baseline in Body Temperature (BT)
时间窗: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in BT (minimum PBC and maximum PBC) are reported.
Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters
时间窗: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Number of participants with at least 2-Grade shift from baseline in laboratory parameters are reported.
Number of Participants With Notable Change in QTcF and QTcB From Baseline
时间窗: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Participants who had notable QTcF and QTcB interval change from baseline are reported.
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: From Day 1 to 28 days after the first dose of study drugs
DLT: Any study drug related Grade (G) 3 or higher toxicity that occurred during DLT evaluation period including: any G\>=3 noninfectious colitis/pneumonitis, liver transaminase elevation (TE) \>=5 but =\<8 upper limit of normal (ULN), any G4 immune-mediated AE (imAE)/immune-related AE (irAE), any G\>=3 clinically significant non-hematologic toxicity, TE \>8 ULN or total bilirubin (TBL) \>5 ULN, increase in AST or ALT \>=3 ULN along with TBL \>=2 ULN, thrombocytopenia (G3/4 associated with G3/higher hemorrhage, G3 that did not improve by at least 1 grade within 7 days, and G4), G4 febrile neutropenia (FN), G3 FN of \>=5 days and G3 FN regardless of duration, G4 neutropenia of \>7 days, G3/4 neutropenia not associated with fever/systemic infection, and anemia (G3 and G4).
Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B
时间窗: Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST V 1.1) guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between.
次要结局
- Percentage of Participants With OR in Exploration Cohorts C2A and C2B(Baseline (-28 to -1 day) through 54.8 months (maximum observed duration))
- Percentage of Participants With Disease Control (DC)(Baseline (-28 to -1 day) through 54.8 months (maximum observed duration))
- Percentage of Participants With DC in Exploration Cohorts (C1A, C1B, C2A, and C2B)(Baseline (-28 to -1 day) through 54.8 months (maximum observed duration))
- Duration of Response (DoR)(Baseline (-28 to -1 day) through 54.8 months (maximum observed duration))
- Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B)(Baseline (-28 to -1 day) through 54.8 weeks (maximum observed duration))
- Percentage of Participants With OR(Baseline (Days -28 to -1) through 54.8 months (maximum observed duration))
- DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B)(Baseline (-28 to -1 day) through 54.8 months (maximum observed duration))
- Overall Survival(Baseline (-28 to -1 day) through 54.8 months (maximum observed duration))
- Minimum Observed Serum Concentration (Cmin) of Monalizumab(Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions)
- Number of Participants With Positive ADA to Durvalumab(Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab))
- Number of Participants With Positive ADA to Cetuximab(Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 9 [if EOT occurred], and 13, and 30 days after the last dose of monalizumab))
- Progression-Free Survival (PFS)(Baseline (-28 to -1 day) through 54.8 months (maximum observed duration))
- Maximum Observed Serum Concentration (Cmax) of Monalizumab(Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions)
- Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B)(Baseline (-28 to -1 day) through 54.8 months (maximum observed duration))
- Serum Concentration of Durvalumab(Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, 13, and 25 and post-dose (POST) on Day 1 of Weeks 1 and 13)
- Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab(Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab))
- Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies(Screening (Days -28 to -1))
- Serum Concentration of Cetuximab(Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, and 13 and post-dose (POST) on Day 1 of Weeks 1, 5, and 13)
- Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies(Screening (Days -28 to -1))