An Open-Label, Multicenter, Phase II Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa (RO6874281), an Immunocytokine, Consisting of Interleukin-2 Variant (IL-2v) Targeting Fibroblast Activation Protein-Α (FAP), in Combination With Atezolizumab (Anti-PD-L1), Administered Intravenously, in Participants With Advanced and/or Metastatic Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 256
- 试验地点
- 44
- 主要终点
- Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
研究概览
简要总结
This is an open-label, multicenter, basket trial Phase II study to evaluate the antitumor activity of simlukafusp alfa in combination with atezolizumab in participants with advanced and/or metastatic solid tumors. Currently the focus is on participants with Head and Neck, oesophageal and cervical cancers with confirmed squamous cell carcinoma histology type.
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
- •Participants who have progressed on at least one previous regimen of anticancer therapy (chemotherapy, mutation targeted therapy, and/or CPI therapy)
- •Measurable disease, as defined by RECIST Version 1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or Karnofsky Performance Score greater than or equal to (>=) 70
- •Life expectancy of >=12 weeks
- •Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the treating physician.
- •Biopsies are not applicable to participants in Cohorts G, H, K, and L presenting with a single target lesion and absence of any non-target lesion.
- •Consent to provide an archival tumor tissue sample (if available, applicable to all participants)
- •Willingness to undergo baseline and on-treatment tumor biopsies for pharmacodynamics (PD) biomarker analysis (biopsies are optional for Cohort A)
- •Adequate cardiovascular function as defined in the study protocol
- •AEs related to any previous radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade less than or equal to (<=) 1, except alopecia (any grade) and Grade 2 peripheral neuropathy
- •Adequate haematological, liver, and renal functions.
- •Participants with unilateral pleural effusion (indications other than NSCLC) are eligible if they fulfill both of the following:
- •NYHA Class 1
- •Forced expiratory volume 1 (FEV1) and forced vital capacity (FVC) >70% of predicted value; participants with lung metastases should present with DLCO >60% of predicted value.
- •Participants with Gilbert's syndrome will be eligible for the study
- •Participants must have had confirmed diagnosis of recurrent or metastatic squamous cell carcinoma head and neck, or esophageal cancer or metastatic, persistent or recurrent squamous cervical cancer.
排除标准
- •Symptomatic or untreated central nervous system (CNS) metastases
- •History of treated asymptomatic CNS metastases as described in the protocol
- •Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks before enrollment
- •Leptomeningeal disease
- •An active second malignancy
- •Penetrating tumor infiltration
- •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
- •Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration
- •History of significant vascular disease (for example, aortic aneurysm, aortic dissection)
- •Active or uncontrolled infections
- •Human immunodeficiency virus (HIV) or Active Hepatitis A, B, C, D or E infection (HAV/HBV/HCV/HDV/HEV).
- •Severe infection within 4 weeks before study treatment administration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- •History of chronic liver disease or evidence of hepatic cirrhosis
- •Dementia or altered mental status that would prohibit informed consent
- •History of, active or suspicion of autoimmune disease
- •History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- •Bilateral pleural effusion confirmed by X-ray
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
- •Concurrent therapy with any other investigational drug
- •Immunomodulating agents as described in study protocol
- •Chronic use of steroids
- •Last dose with any cytostatic treatments < 28 days before study treatment administration
- •Radiotherapy within the last 4 weeks before start of study treatment administration, with the exception of limited field palliative radiotherapy
- •Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1 or at any time during the study and 5 months after the last dose of atezolizumab
- •Major surgery or significant traumatic injury <28 days before study treatment administration (excluding fine needle biopsies) or if wound healing has not completed after surgery or anticipation of the need for major surgery during study treatment
- •Known hypersensitivity to any of the components of the simlukafusp alfa drug product or atezolizumab drug product
- •Severe dyspnea at rest or requiring supplementary oxygen therapy Locally curative options are available for participant's disease.
研究组 & 干预措施
Cohort A (Part I)
Checkpoint Inhibitor (CPI)-Naïve Participants with non-small-cell lung cancer (NSCLC) who have not received CPI therapy previously will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: collection of fresh tumor biopsies (at baseline and on-treatment) will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort A (Part I)
Checkpoint Inhibitor (CPI)-Naïve Participants with non-small-cell lung cancer (NSCLC) who have not received CPI therapy previously will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: collection of fresh tumor biopsies (at baseline and on-treatment) will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort B (Part I)
CPI-Experienced Participants (NSCLC) who have received CPI therapy previously will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort B (Part I)
CPI-Experienced Participants (NSCLC) who have received CPI therapy previously will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg. Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort C (Part I)
This is a mandatory biopsy cohort based on the treatment's safety and preliminary activity analysis to enroll CPI-Naive Participants. Participants (NSCLC) will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort C (Part I)
This is a mandatory biopsy cohort based on the treatment's safety and preliminary activity analysis to enroll CPI-Naive Participants. Participants (NSCLC) will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort D Arm I (Part I)
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel.
Participants will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort D Arm I (Part I)
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel.
Participants will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort D Arm 2 (Part I)
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel.
Participants will receive simlukafusp alfa intravenous (IV) infusion once in 3 weeks (Q3W) up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q3W at a dose of 1200 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort D Arm 2 (Part I)
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel.
Participants will receive simlukafusp alfa intravenous (IV) infusion once in 3 weeks (Q3W) up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q3W at a dose of 1200 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort D Arm 3 (Part I)
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel will receive a single-agent gemcitabine or vinorelbine as per approved protocol.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: Gemcitabine (Drug)
Cohort D Arm 3 (Part I)
CPI Experienced Participants (NSCLC) who were previously treated with platinum and docetaxel will receive a single-agent gemcitabine or vinorelbine as per approved protocol.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: Vinorelbine (Drug)
Cohort E Arm I (Part II)
This cohort will enroll participants (NSCLC) with High-Tumor PD-L1 Expression who have not received any prior systemic therapy. Participants will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort E Arm I (Part II)
This cohort will enroll participants (NSCLC) with High-Tumor PD-L1 Expression who have not received any prior systemic therapy. Participants will receive simlukafusp alfa intravenous (IV) infusion once in a week (QW) for first 5 doses, and once in 2 weeks (Q2W) for remaining doses up to maximum 36 months. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered in combination Q2W at a dose of 840 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort E Arm 2 (Part II)
This cohort will enroll participants (NSCLC) with High-Tumor PD-L1 Expression who have not received any prior systemic therapy. Participants will receive simlukafusp alfa IV infusion in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort E Arm 2 (Part II)
This cohort will enroll participants (NSCLC) with High-Tumor PD-L1 Expression who have not received any prior systemic therapy. Participants will receive simlukafusp alfa IV infusion in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg.
Tumor biopsies: 2 mandatory fresh tumor biopsies, one at baseline and one on-treatment, will be collected. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort F (Part I)
CPI-experienced, docetaxel naive participants (NSCLC) who experienced disease progression during or following treatment with a platinum - containing regimen. Participants will receive combination of simlukafusp alfa and atezolizumab in a Q3W schedule. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg.
Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort F (Part I)
CPI-experienced, docetaxel naive participants (NSCLC) who experienced disease progression during or following treatment with a platinum - containing regimen. Participants will receive combination of simlukafusp alfa and atezolizumab in a Q3W schedule. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg.
Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort G (Part III)
CPI-naïve SCC of the head and neck (SCCHN) (20 response-evaluable participants), mandatory biopsies. Participants in cohort G Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
干预措施: simlukafusp alfa (Drug)
Cohort G (Part III)
CPI-naïve SCC of the head and neck (SCCHN) (20 response-evaluable participants), mandatory biopsies. Participants in cohort G Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort H (Part III)
Previously treated, CPI-experienced squamous cell carcinoma head and heck cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort H Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
干预措施: simlukafusp alfa (Drug)
Cohort H (Part III)
Previously treated, CPI-experienced squamous cell carcinoma head and heck cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort H Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort I (Part III)
Previously treated, CPI-naïve squamous esophageal cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort I Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort I (Part III)
Previously treated, CPI-naïve squamous esophageal cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort I Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort J (Part III)
Previously treated, CPI-naïve squamous cervical cancer (20 response evaluable participants): mandatory biopsy. Participants in cohort J Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort J (Part III)
Previously treated, CPI-naïve squamous cervical cancer (20 response evaluable participants): mandatory biopsy. Participants in cohort J Part III will receive simlukafusp alfa Q3W in combination with atezolizumab Q3W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 1200 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort K (Part III)
CPI-naïve SCC of the head and neck (SCCHN) (20 response-evaluable participants), mandatory biopsies. Participants in cohort K Part III will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
干预措施: simlukafusp alfa (Drug)
Cohort K (Part III)
CPI-naïve SCC of the head and neck (SCCHN) (20 response-evaluable participants), mandatory biopsies. Participants in cohort K Part III will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort L (Part III)
Previously treated, CPI-experienced squamous cell carcinoma head and neck cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort L Part III will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
干预措施: simlukafusp alfa (Drug)
Cohort L (Part III)
Previously treated, CPI-experienced squamous cell carcinoma head and neck cancer (20 response evaluable participants), mandatory biopsies. Participants in cohort L Part III will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional. Biopsies are not applicable to participants presenting with a single target lesion and absence of any non-target lesion.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort M (Part III)
Esophageal SCC participants will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort M (Part III)
Esophageal SCC participants will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Cohort N (Part III)
Cervical SCC participants will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: simlukafusp alfa (Drug)
Cohort N (Part III)
Cervical SCC participants will receive simlukafusp alfa QW in combination with atezolizumab Q2W for 4 weeks followed by simlukafusp alfa in combination with atezolizumab Q2W. Simlukafusp alfa will be administered at a 10 mg flat dose. Atezolizumab IV infusion will be administered at a dose of 840 mg. Tumor biopsies: one mandatory fresh tumor biopsy will be collected at baseline. Additional on-treatment biopsies will be optional.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
结局指标
主要结局
Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: Baseline up to disease progression or study treatment discontinuation (up to 38 months)
ORR was defined as the percentage of participants with observed tumor response of complete response (CR), or partial response (PR) determined according to RECIST version 1.1. CR was defined as the disappearance of all target lesions with reduction in target/non-target pathological lymph nodes to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The percentages of participants are rounded off to the nearest single decimal point.
次要结局
- Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1(Baseline up to disease progression or study treatment discontinuation (up to 38 months))
- Duration of Response (DoR) According to RECIST Version 1.1(From first occurrence of documented CR or PR up to disease progression or study treatment discontinuation (assessed every 8 weeks after study treatment start for the first year, and every 12 weeks thereafter, up to 38 months))
- Progression-Free Survival (PFS) According to RECIST Version 1.1(Study treatment initiation up to disease progression or study treatment discontinuation (up to 38 months))
- Overall Survival (OS)(From first dose of study treatment up to death due to any cause (up to approximately 47 months))
- Percentage of Participants With Adverse Events (AEs)(Baseline up to end of the study (up to approximately 47 months))
- Percentage of Participants by Programmed Death-Ligand 1 (PD-L1) Status According to Immunohistochemical Methods(Baseline)
- Change From Baseline in Density of Cluster of Differentiation (CD) 8 Positive (CD8+) Cells According to Immunohistochemical Methods(Baseline up 2 months)
- Change From Baseline in Density of Cluster of Differentiation 3 Negative (CD3-) Perforin Positive Cells According to Immunohistochemical Methods(Baseline up to 2 months)
- Change From Baseline in Density of PD-L1 According to Immunohistochemical Methods(Baseline up to 2 months)