A Phase 1b/2 Open Label Umbrella Study of Sasanlimab Combined With Anti-Cancer Therapies Targeting Multiple Molecular Mechanisms in Participants With Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 34
- 试验地点
- 59
- 主要终点
- Phase 2 Sub-Study B: Objective Response Rate
研究概览
简要总结
Phase 1b/Phase 2 Umbrella Study; open-label, multi-center, parallel group study.
Sasanlimab (a PD-1 antagonist monoclonal antibody) will be combined with a different targeted therapy in each sub-study. Phase1b of each sub-study will evaluate the safety of the combination and select the dose for the Phase 2 portion. Phase 2 of each sub-study will evaluate the anti-tumor activity of the combination.
Sub-Study A is active, not recruiting, ongoing participants are still receiving treatment in Phase 1, Phase 2 will not be initiated.
Sub-study B is complete. All participants have discontinued treatment and any additional follow up required by protocol.
详细描述
Landscape 1011 is a clinical research study for people with advanced (stage 3b or 4) non-small cell lung cancer (NSCLC). The purpose of this study is to learn if the study medicine (sasanlimab, a type of immunotherapy) along with other study medicines is safe and effective in people with non-small cell lung cancer that has spread outside of the lungs. There are currently two sub-studies using different types of medicines. People in the first sub-study will receive sasanlimab as a subcutaneous (under the skin) injection at the study clinic every 4 weeks. Additionally, they will take targeted cancer therapies encorafenib by mouth once a day and binimetinib by mouth twice a day at home.
People in the second sub-study will receive the study medicine sasanlimab as a subcutaneous (under the skin) injection at the study clinic every 3 weeks and will also receive SEA-TGT (an immunotherapy) by infusion every three weeks.
Additionally, they will take axitinib (a targeted therapy) by mouth twice a day at home.
In addition to taking the study drugs, participants in the sub-studies will be asked to visit the clinic for health checks. These include health questions, physical examinations, blood and urine samples, and imaging scans. These assessments help the study doctor and team to monitor the participants' safety and well-being, and to see how their cancer is responding to the treatment. Participants will continue in the study until the cancer is no longer responding to the study medicine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Umbrella Phase 1b & 2:
- •Histologically or cytologically confirmed locally advanced/metastatic (Stage IIIB-IV) NSCLC.
- •At least one measurable lesion per RECIST v1.1 at Screening.
- •ECOG Performance Status 0 or
- •Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤
- •Adequate hepatic, renal, and bone marrow function.
- •Additional Inclusion Criteria for Sub-Study A Phase 1b &2:
- •BRAFV600E mutation in tumor tissue or plasma as determined by a local laboratory PCR or NGS assay and documented in a local pathology report.
- •Additional Inclusion Criteria for Sub-Study A Phase 1b only:
- •Any line of therapy for locally advanced/metastatic NSCLC.
- •Additional Inclusion Criteria for Sub-Study A Phase 2 only:
- •Previously untreated for locally advanced/metastatic NSCLC
- •Additional Inclusion Criteria for Sub-Study B Phase 1b only::
- •Any line of therapy for locally advanced/metastatic NSCLC.
- •Additional Inclusion Criteria for Sub-Study B Phase 2 only:
- •Previously untreated for locally advanced/metastatic NSCLC (Arms B1 & B2), or
- •One or 2 prior lines of therapy for advanced/metastatic NSCLC (Arm B3), including immune checkpoint inhibitor treatment + chemotherapy, and have progressed during or after that therapy.
- •PD-L1 TPS ≥1%
排除标准
- •Umbrella Phase 1b &2:
- •Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
- •Active non-infectious pneumonitis, pulmonary fibrosis, or known history of immune-mediated pneumonitis.
- •Active infection requiring systemic therapy.
- •Clinically significant cardiovascular disease.
- •Other malignancy within 2 years of first dose, with exceptions.
- •Symptomatic brain metastasis, with exceptions.
- •Additional Exclusion Criteria for Sub-Study A Phase 1b&2:
- •EGFR mutation, ALK fusion oncogene, or ROS1 rearrangement.
- •Prior treatment with any BRAF inhibitor or MEK inhibitor.
- •Additional Exclusion Criteria for Sub-Study A Phase 2 only:
- •Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.
- •Additional Exclusion Criteria for Sub-Study B Phase 1b&2:
- •Documentation of any tumor-driving molecular alteration (eg, BRAF, EGFR, ALK)
- •Additional Exclusion Criteria for Sub-Study B Phase 2 only:
- •Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.(Arms B1 & B2)
- •Confirmed progressive disease on 1st or 2nd imaging tumor assessment after initiation of therapy for advanced/metastatic NSCLC.
研究组 & 干预措施
Sub-Study A
Sasanlimab will be administered subcutaneously. Encorafenib & binimetinib will be administered orally. Treatments will be administered until progressive disease, unacceptable AE, participant withdraws, or study is terminated.
干预措施: Sasanlimab Prefilled syringe (Drug)
Sub-Study B
Sasanlimab will be administered subcutaneously. Axitinib will be administered orally. SEA-TGT will be administered intravenously. Treatments will be administered until progressive disease, unacceptable AE, patient withdraws, or study is terminated.
干预措施: SEA-TGT (Drug)
Sub-Study B
Sasanlimab will be administered subcutaneously. Axitinib will be administered orally. SEA-TGT will be administered intravenously. Treatments will be administered until progressive disease, unacceptable AE, patient withdraws, or study is terminated.
干预措施: Sasanlimab (Drug)
Sub-Study A
Sasanlimab will be administered subcutaneously. Encorafenib & binimetinib will be administered orally. Treatments will be administered until progressive disease, unacceptable AE, participant withdraws, or study is terminated.
干预措施: Encorafenib (Drug)
Sub-Study A
Sasanlimab will be administered subcutaneously. Encorafenib & binimetinib will be administered orally. Treatments will be administered until progressive disease, unacceptable AE, participant withdraws, or study is terminated.
干预措施: Binimetinib (Drug)
Sub-Study B
Sasanlimab will be administered subcutaneously. Axitinib will be administered orally. SEA-TGT will be administered intravenously. Treatments will be administered until progressive disease, unacceptable AE, patient withdraws, or study is terminated.
干预措施: Axitinib (Drug)
结局指标
主要结局
Phase 2 Sub-Study B: Objective Response Rate
时间窗: From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy (maximum of 21 months)
ORR was defined as percentage of participants with confirmed CR or PR according to RECIST v1.1 based on investigator assessment, from the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy. CR was defined as complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 millimeter \[mm\]). PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm.
Phase 1b of Sub-Study A: Percentage of Participants With Dose-Limiting Toxicities (DLT)
时间窗: Day 1 up to Day 28 of Cycle 1
DLT=AEs in DLT observation period (OP) related to any study intervention:Grade (G)4 neutropenia;thrombocytopenia or anemia;febrile neutropenia;neutropenic infection;G3 thrombocytopenia with bleeding. Any G\>=3 toxicity (except transient G3 fatigue, local reactions/headache that resolved to G\<=1/baseline; G3 nausea, vomiting controlled within 72 hrs, G3 hypertension controlled by medical therapy (MT), G3 diarrhea that improved to G\<=2 within 72 hrs, G3 skin toxicity that resolved to G\<=1 in \<7 days after MT, G3 endocrinopathies controlled by MT and tumors flare); Non-hematologic G3 lab abnormality \[LA\](medical intervention or hospitalization), or any G4 LA;ALT/AST\>3\*ULN (normal at baseline) or \>3\*ULN and doubling baseline (\>ULN at baseline) and associated with total bilirubin(TB) \>2\*ULN;or ALT/AST\>5\*ULN; or TB\>3\*ULN. Missing 75% of planned doses during DLT OP due to treatment-related toxicities. AE not listed/DLT criteria outside DLT OP was DLT at discretion of sponsor and investigator.
Phase 2 of Sub-Study A: Durable Objective Response Rate (ORR)
时间窗: From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy
Durable ORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 based on investigator assessment, lasting for at least 10 months from the date of first CR or PR until the date of the first documentation of disease progression (PD), death, or start of new anticancer therapy. CR was defined as complete disappearance of all target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 millimeter \[mm\]). PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in sum of diameters of target measurable lesions above smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm.
Phase 1b of Sub-Study B: Percentage of Participants With DLT
时间窗: Day 1 up to Day 21 of Cycle 1
DLT=AEs in DLT OP related to any study intervention: G4 neutropenia; thrombocytopenia or anemia; neutropenia; neutropenic infection; G3 thrombocytopenia with bleeding. Any G\>=3 toxicity (except transient G3 fatigue, local reactions/headache that resolved to G\<=1/baseline; G3 nausea, vomiting controlled within 72 hrs, G3 hypertension controlled by MT, G3 diarrhea that improved to G\<=2 within 72 hrs, G3 skin toxicity that resolved to G\<=1 in \<7 days after MT, G3 endocrinopathies controlled by MT and tumors flare); Non-hematologic G3 LA (medical intervention or hospitalization), or any G4 LA;ALT/AST\>3\*ULN (normal at baseline) or \>3\*ULN and doubling baseline (\>ULN at baseline) and associated with TB \>2\*ULN; or ALT/AST\>5\*ULN; or TB\>3\*ULN. Missing 75% of planned doses during DLT OP due to treatment-related toxicities. AE not listed/DLT criteria outside DLT OP was DLT at discretion of sponsor and investigator.
次要结局
- Phase 2 of Sub-Study A: Duration of Response (DR)(From the date of first documentation of OR to the date of the first documentation of PD or death due to any cause, whichever occurred first)
- Phase 2 of Sub-Study A: Time to Tumor Response (TTR)(From the date of first dose of study treatment to the date of first documentation of objective response)
- Phase 2 of Sub-Study A: Overall Survival (OS)(From the date of first dose of study treatment to the date of death due to any cause or censoring date)
- Phase 2 of Sub-Study A: Progression-Free Survival (PFS)(From the date of first dose of study treatment to the date of first documentation of PD or death due to any cause, whichever occurred first)
- Phase 1b of Sub-Study A: Maximum Observed Plasma Concentration (Cmax) of Sasanlimab(Cycle 1 (pre-dose on Day 1, 168 hours [Day 8],336 hours [Day 15] and Day 28 post-dose) and Cycle 5 (pre-dose on Day 1 and 168 hours [Day 8] post dose) (1 cycle= 28 days))
- Phase 2 of Sub-Study A: Ctrough of Encorafenib(Cycle 5 Day 1 (pre-dose))
- Phase 1b of Sub-Study A: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab(Cycle 1 (pre-dose on Day 1, 168 hours [Day 8] and 336 hours [Day 15] and Day 28 post-dose) (1 cycle= 28 days))
- Phase 2 of Sub-Study A: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUCtau) After Single Dose of Sasanlimab(Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) (1 cycle= 28 days))
- Phase 1b of Sub-Study B: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months))
- Phase 2 of Sub-Study B: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months))
- Phase 1b of Sub-Study B: Number of Participants With Shift From Baseline in Hematology Parameters Values Based on CTCAE V5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 39.3 months; maximum follow-up approximately 39.66 months))
- Phase 2 of Sub-Study A: Maximum Observed Plasma Concentration (Cmax) of Sasanlimab(Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 Day 1 (pre-dose) (1 cycle= 28 days))
- Phase 1b of Sub-Study A: Time for Cmax (Tmax) of Sasanlimab(Cycle 1 (pre-dose on Day 1, 168 hours [Day 8], 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 (pre-dose on Day 1 and 168 hours [Day 8] post dose) (1 cycle= 28 days))
- Phase 2 of Sub-Study A: Time for Cmax (Tmax) of Sasanlimab(Cycle 1 (pre-dose on Day 1, 336 hours [Day 15] and Day 28 post-dose) and Cycle 5 Day 1 (pre-dose) (1 cycle= 28 days))
- Phase 1b of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab(Cycle 5 Day 1 (pre-dose) (1 cycle= 28 days))
- Phase 2 of Sub-Study A: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab(Cycle 5 Day 1 (pre-dose) (1 cycle= 28 days))
- Phase 1b of Sub-Study A: Ctrough of Encorafenib(Day 1 (pre-dose) of Cycle 1, 2 and 5; Day 15 of Cycle 1 (1 cycle= 28 days))
- Phase 1b of Sub-Study A: Ctrough of Binimetinib(Day 1 (pre-dose) of Cycles 1, 2, and 5 (1 cycle= 28 days))
- Phase 2 of Sub-Study A: Ctrough of Binimetinib(Cycle 5 Day 1 (pre-dose))
- Phase 1b of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab(Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 255 days) (1 cycle= 28 days))
- Phase 2 of Sub-Study A: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) Score(Baseline up to end of treatment)
- Phase 2 of Sub-Study A: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against Sasanlimab(Pre-dose on Cycle 1 Day 1 until end of treatment)
- Phase 2 of Sub-Study A: Objective Response (OR) Rate by Programmed Death Ligand-1 (PD-L1) Expression at Baseline(From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy)
- Phase 2 of Sub-Study A: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) Score(Baseline up to end of treatment)
- Phase 1b of Sub-Study B: Number of Participants With Shift From Baseline in Chemistry Parameters Values Based on CTCAE V5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months))
- Phase 2 of Sub-Study B: Number of Participants With Shift From Baseline in Hematology Parameter Values Based on CTCAE V5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months))
- Phase 2 of Sub-Study B: Number of Participants With Shift From Baseline in Chemistry Parameter Values Based on CTCAE V5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months))
- Phase 1b of Sub-Study B: Objective Response Rate(From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy, whichever occurred first (maximum of 21 months))
- Phase 1b of Sub-Study B: Duration of Response (DR)(From the date of first documentation of OR to the date of first documentation of PD or death, whichever occurred first (maximum of 21 months))
- Phase 1b of Sub-Study B: Time to Tumor Response (TTR)(From the date of first dose of study treatment to the date of first documentation of objective response (CR or PR) (maximum of 21 months))
- Phase 1b of Sub-Study B: Progression-Free Survival (PFS)(From the date of first dose of study treatment to the date of first documentation of PD or death due to any cause, whichever occurred first (maximum of 21 months))
- Phase 2 of Sub-Study B: Duration of Response (DR)(From date of first documentation of OR to the date of first documentation of PD or death, whichever occurred first (maximum of 21 months))
- Phase 2 of Sub-Study B: Time to Tumor Response (TTR)(From the date of first dose of study treatment to the date of first documentation of objective response (CR or PR) (maximum of 21 months))
- Phase 2 of Sub-Study B: Progression-Free Survival (PFS)(From the date of first dose of study treatment to the date of first documentation of PD or death due to any cause, whichever occurred first (maximum of 21 months))
- Phase 2 of Sub-Study B: Overall Survival (OS)(From the date of first dose of study treatment to the date of death due to any cause or censoring date, whichever occurred first (maximum of 21 months))
- Phase 1b of Sub-Study B: Cmax of Sasanlimab(Cycle 1: pre-dose, 168 hours post-dose on Day 1, Cycle 5: pre-dose, 168 hours post-dose on Day 1 (1 cycle= 21 days))
- Phase 1b of Sub-Study B: Cmax of SEA-TGT(Cycle 1: pre-dose, 168 hours post-dose on Day 1, Cycle 5: pre-dose, 168 hours post-dose on Day 1 (1 cycle= 21 days))
- Phase 2 of Sub-Study B: Cmax of Sasanlimab(Cycle 1: pre-dose, 168 hours post-dose on Day 1, Cycle 5: pre-dose, 168 hours post-dose on Day 1 (1 cycle= 21 days))
- Phase 1b of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of Axitinib(Pre-dose on Cycle 1 Day 1 and Day 8; pre-dose on Cycle 5 Day 1 and Day 8 (1 cycle= 21 days))
- Phase 1b of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of SEA-TGT(Pre-dose on Cycle 1 Day 1; pre-dose on Cycle 5 Day 1 (1 cycle= 21 days))
- Phase 1b of Sub-Study B: Cmax of Axitinib(Cycle 1: pre-dose on Day 1, Day 8 and 3 hours post-dose on Day 1; Cycle 5: pre-dose on Day 1, Day 8 and 3 hours post-dose on Day 1 (1 cycle= 21 days))
- Phase 2 of Sub-Study B: Cmax of Axitinib(Cycle 1: pre-dose on Day 1, Day 8 and 3 hours post-dose on Day 1; Cycle 5: pre-dose on Day 1, Day 8 and 3 hours post-dose on Day 1 (1 cycle= 21 days))
- Phase 2 of Sub-Study B: Cmax of SEA-TGT(Cycle 1: pre-dose, 168 hours post-dose on Day 1, Cycle 5: pre-dose, 168 hours post-dose on Day 1 (1 cycle= 21 days))
- Phase 2 of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab(Cycle 1: pre-dose on Day 1, Cycle 5: pre-dose on Day 1 (1 cycle= 21 days))
- Phase 2 of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of SEA-TGT(Pre-dose on Cycle 1 Day 1; pre-dose on Cycle 5 Day 1 (1 cycle= 21 days))
- Phase 1b of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of Sasanlimab(Pre-dose on Cycle 1 Day 1 and Cycle 5 Day 1 (1 cycle= 21 days))
- Phase 2 of Sub-Study B: Number of Participants With Positive Anti-Drug Antibody (ADA) Against Sasanlimab and SEA-TGT(Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 21 months) (1 cycle= 21 days))
- Phase 2 of Sub-Study B: Pre-dose Concentration During Multiple Dosing (Ctrough) of Axitinib(Pre-dose on Cycle 1 Day 1 and Day 8; pre-dose on Cycle 5 Day 1 and Day 8 (1 cycle= 21 days))
- Phase 1b of Sub-Study B: Number of Participants With Positive Anti-Drug Antibody (ADA) Against Sasanlimab and SEA-TGT(Pre-dose on Cycle 1 Day 1 until end of treatment (up to approximately 21 months) (1 cycle= 21 days))
- Phase 2 of Sub-Study B: Objective Response Rate by PD-L1 Expression in Available Tumor Tissue(From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy (maximum of 21 months))
- Phase 2 of Sub-Study A: Number of Participants With Adverse Events Graded According to NCI-CTCAE Version 5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment)
- Phase 1b of Sub-Study A: Objective Response Rate(From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy (approximately 38.66 months))
- Phase 1b of Sub-Study A: Number of Participants With Adverse Events (AEs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months))
- Phase 1b of Sub-Study A: Number of Participants With Shift From Baseline in Hematology Parameters Values Based on CTCAE V5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months))
- Phase 2 of Sub-Study A: Number of Participants With Laboratory Abnormalities(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment)
- Phase 1b of Sub-Study A: Durable Objective Response Rate (ORR)(From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy (approximately 38.66 months))
- Phase 1b of Sub-Study A: Number of Participants With Shift From Baseline in Chemistry Parameters Values Based on CTCAE V5.0(From the start of study treatment (Cycle1 Day1) up to 30 days after last dose of study treatment (maximum exposure = 38.66 months; maximum follow-up approximately 39.66 months))
- Phase 2 of Sub-Study A: Objective Response Rate(From the date of first CR or PR until the date of the first documentation of PD, death, or start of new anticancer therapy)