Basket Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa as a Combination Therapy in Participants With Advanced and/or Metastatic Solid Tumors

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers
• Intervention / Treatment: Drug: simlukafusp alfa; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Drug: Gemcitabine; Drug: Vinorelbine

• Study Type: Interventional
• Enrollment (Actual): 256
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Marseille, France, 13385
    • Hopital Timone Adultes; Oncologie Medicale Et Usp
  • Montpellier cedex 5, France, 34298
    • ICM; Medecine B3
  • Villejuif, France, 94805
    • Gustave Roussy Cancer Campus
• Germany
  • Essen, Germany, 45147
    • Universitätsklinikum Essen; Innere Klinik (Tumorforschung)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center; Oncology
• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 003-722
    • Severance Hospital, Yonsei University Health System
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital; Clinical Oncology
• Poland
  • Gda?sk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz
• Russian Federation
  • Moscow, Russian Federation, 105229
    • N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
  • Saint-Petersburg, Russian Federation, 197758
    • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
• Singapore
  • Singapore, Singapore, 119228
    • National University Hospital; National University Cancer Institute, Singapore (NCIS)
  • Singapore, Singapore, 169610
    • National Cancer Centre; Medical Oncology
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Oncologia
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra Madrid; Servicio de Oncología
  • Madrid, Spain, 28040
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra
• Switzerland
  • Geneve, Switzerland, 1211
    • Hôpitaux Universit. de Genève Médecine Oncologie; Oncologie
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung Uni Hospital; Dept of Hematology and Oncology
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; Dept of Oncology
• Turkey
  • Adana, Turkey, 01120
    • Adana Baskent University Hospital; Medical Oncology
  • Antalya, Turkey, 07070
    • Akdeniz University Medical Faculty; Medical Oncology Department
  • Edirne, Turkey, 22030
    • Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty; Medikal Onkoloji Departmani
  • Izmir, Turkey
    • ?zmir Medical Park; Onkoloji
  • Kadiköy, Turkey, 34722
    • Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology
• United Kingdom
  • London, United Kingdom, N7 9NH
    • University College London Hospital
  • London, United Kingdom, EC1M6BQ
    • Barts
  • Manchester, United Kingdom, M2O 4BX
    • Christie Hospital Nhs Trust; Medical Oncology
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Institute of Cancer Research
• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Cancer Treatment Centers of America

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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:

  1. NYHA Class 1
  2. 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

17

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: Gemcitabine; Single-agent treatment administered as per approved protocol.; Drug: Vinorelbine; Single-agent treatment administered as per approved protocol.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
Experimental: 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.	Drug: simlukafusp alfa; simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.; Other Names: RO6874281; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	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.	Baseline up to disease progression or study treatment discontinuation (up to 38 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1	DCR was defined as the percentage of participants with observed tumor response of CR, PR or stable disease (SD) 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 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. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir). The percentages of participants are rounded off to the nearest single decimal point.	Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Duration of Response (DoR) According to RECIST Version 1.1	DoR was determined for participants who had a best overall response of CR or PR. CR was defined as the disappearance of all target lesions with a reduction in target/non-target pathological lymph nodes to < 10 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. DoR was defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.	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	PFS was defined as the time from study treatment initiation (Cycle 1 Day 1 [1 cycle=14 days for QW/Q2W cohorts; 1 cycle=21 days for Q3W cohorts]) to the first occurrence of documented disease progression (based on Investigator's assessment) or death from any cause during treatment, whichever occurs first. Participants that did not have documented progressive disease or death during the study were censored at the day of the last tumor assessment.	Study treatment initiation up to disease progression or study treatment discontinuation (up to 38 months)
Overall Survival (OS)	OS was defined as the time from the first dose of study treatment to the time of death from any cause on study. Participants who were still alive at the time of analysis were censored at the last date known alive.	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)	An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2018
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: December 22, 2017
• First Submitted That Met QC Criteria: December 22, 2017
• First Posted (Actual): December 29, 2017

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Antibodies; Vinorelbine; Atezolizumab
• Other Study ID Numbers: BP40234; 2017-003182-94 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No