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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03386721




Registration number
NCT03386721
Ethics application status
Date submitted
22/12/2017
Date registered
29/12/2017

Titles & IDs
Public title
Basket Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa as a Combination Therapy in Participants With Advanced and/or Metastatic Solid Tumors
Scientific title
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-? (FAP), in Combination With Atezolizumab (Anti-PD-L1), Administered Intravenously, in Participants With Advanced and/or Metastatic Solid Tumors
Secondary ID [1] 0 0
2017-003182-94
Secondary ID [2] 0 0
BP40234
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - simlukafusp alfa
Treatment: Drugs - Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Vinorelbine

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.


Treatment: Drugs: simlukafusp alfa
simlukafusp alfa will be administered as per the dosage regimen mentioned in arm descriptions.

Treatment: Drugs: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Atezolizumab will be administered as per the dosage regimen mentioned in arm descriptions.

Treatment: Drugs: Gemcitabine
Single-agent treatment administered as per approved protocol.

Treatment: Drugs: Vinorelbine
Single-agent treatment administered as per approved protocol.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Timepoint [1] 0 0
Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Secondary outcome [1] 0 0
Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1
Timepoint [1] 0 0
Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Secondary outcome [2] 0 0
Duration of Response (DoR) According to RECIST Version 1.1
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Progression-Free Survival (PFS) According to RECIST Version 1.1
Timepoint [3] 0 0
Study treatment initiation up to disease progression or study treatment discontinuation (up to 38 months)
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
From first dose of study treatment up to death due to any cause (up to approximately 47 months)
Secondary outcome [5] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [5] 0 0
Baseline up to end of the study (up to approximately 47 months)
Secondary outcome [6] 0 0
Percentage of Participants by Programmed Death-Ligand 1 (PD-L1) Status According to Immunohistochemical Methods
Timepoint [6] 0 0
Baseline
Secondary outcome [7] 0 0
Change From Baseline in Density of Cluster of Differentiation (CD) 8 Positive (CD8+) Cells According to Immunohistochemical Methods
Timepoint [7] 0 0
Baseline up 2 months
Secondary outcome [8] 0 0
Change From Baseline in Density of Cluster of Differentiation 3 Negative (CD3-) Perforin Positive Cells According to Immunohistochemical Methods
Timepoint [8] 0 0
Baseline up to 2 months
Secondary outcome [9] 0 0
Change From Baseline in Density of PD-L1 According to Immunohistochemical Methods
Timepoint [9] 0 0
Baseline up to 2 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/12/2021
Sample size
Target
Accrual to date
Final
256
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
Belgium
State/province [3] 0 0
Edegem
Country [4] 0 0
Belgium
State/province [4] 0 0
Gent
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
France
State/province [6] 0 0
Bordeaux
Country [7] 0 0
France
State/province [7] 0 0
Marseille
Country [8] 0 0
France
State/province [8] 0 0
Montpellier cedex 5
Country [9] 0 0
France
State/province [9] 0 0
Villejuif
Country [10] 0 0
Germany
State/province [10] 0 0
Essen
Country [11] 0 0
Israel
State/province [11] 0 0
Haifa
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Seongnam-si
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Seoul
Country [14] 0 0
New Zealand
State/province [14] 0 0
Auckland
Country [15] 0 0
Poland
State/province [15] 0 0
Gda?sk
Country [16] 0 0
Poland
State/province [16] 0 0
Warszawa
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Moscow
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Saint-Petersburg
Country [19] 0 0
Singapore
State/province [19] 0 0
Singapore
Country [20] 0 0
Spain
State/province [20] 0 0
Navarra
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Valencia
Country [24] 0 0
Switzerland
State/province [24] 0 0
Geneve
Country [25] 0 0
Taiwan
State/province [25] 0 0
Tainan
Country [26] 0 0
Taiwan
State/province [26] 0 0
Taipei
Country [27] 0 0
Turkey
State/province [27] 0 0
Adana
Country [28] 0 0
Turkey
State/province [28] 0 0
Antalya
Country [29] 0 0
Turkey
State/province [29] 0 0
Edirne
Country [30] 0 0
Turkey
State/province [30] 0 0
Istanbul
Country [31] 0 0
Turkey
State/province [31] 0 0
Izmir
Country [32] 0 0
Turkey
State/province [32] 0 0
Kadiköy
Country [33] 0 0
United Kingdom
State/province [33] 0 0
London
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Manchester
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03386721