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

Roche

Status and phase: Terminated; Phase 2

Conditions: Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers

Treatments: Drug: Vinorelbine; Drug: simlukafusp alfa; Drug: Gemcitabine; Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Study type: Interventional

Funder types: Industry

Identifiers

NCT03386721

2017-003182-94 (EudraCT Number)

BP40234

Details and patient eligibility

About

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.

Enrollment: 256 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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256 participants in 17 patient groups

Cohort A (Part I)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort B (Part I)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort C (Part I)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort D Arm I (Part I)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort D Arm 2 (Part I)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort D Arm 3 (Part I)

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: Vinorelbine

Cohort E Arm I (Part II)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort E Arm 2 (Part II)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort F (Part I)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort G (Part III)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort H (Part III)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort I (Part III)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort J (Part III)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort K (Part III)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort L (Part III)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort M (Part III)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody

Cohort N (Part III)

Experimental group

Description:

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.

Treatment:

Drug: simlukafusp alfa

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody