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

Conditions

• Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• simlukafusp alfa — DRUG
  simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.
• Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody — DRUG
  Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.
• Gemcitabine — DRUG
  Single-agent treatment administered as per approved protocol.
• Vinorelbine — DRUG
  Single-agent treatment administered as per approved protocol.

Study Details

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.

Key Dates

Start date

Feb 19, 2018

Status verified

Feb 2023

Primary completion

Dec 30, 2021

Completion

Dec 30, 2021

Study Design

Enrollment

256 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Primary Outcome Measure

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

Locations (2)

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