Clinical trial NCT03386721: Basket Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa as a Combination Therapy in Participants With Advanced and/or Metastatic Solid Tumors
Official 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-Α (FAP), in Combination With Atezolizumab (Anti-PD-L1), Administered Intravenously, in Participants With Advanced and/or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-12-29
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Baseline up to disease progression or study treatment discontinuation (up to 38 months)
Secondary outcomes:
measure: Percentage of Participants With Disease Control Rate (DCR) Determined According to RECIST Version 1.1
timeFrame: Baseline up to disease progression or study treatment discontinuation (up to 38 months)
measure: Duration of Response (DoR) According to RECIST Version 1.1
timeFrame: 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)
measure: Progression-Free Survival (PFS) According to RECIST Version 1.1
timeFrame: Study treatment initiation up to disease progression or study treatment discontinuation (up to 38 months)
measure: Overall Survival (OS)
timeFrame: From first dose of study treatment up to death due to any cause (up to approximately 47 months)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to end of the study (up to approximately 47 months)
measure: Percentage of Participants by Programmed Death-Ligand 1 (PD-L1) Status According to Immunohistochemical Methods
timeFrame: Baseline
measure: Change From Baseline in Density of Cluster of Differentiation (CD) 8 Positive (CD8+) Cells According to Immunohistochemical Methods
timeFrame: Baseline up 2 months
measure: Change From Baseline in Density of Cluster of Differentiation 3 Negative (CD3-) Perforin Positive Cells According to Immunohistochemical Methods
timeFrame: Baseline up to 2 months
measure: Change From Baseline in Density of PD-L1 According to Immunohistochemical Methods
timeFrame: Baseline up to 2 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center
state: California
city: Newnan
country: United States
facility: Cancer Treatment Centers of America
state: Georgia
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Bordeaux
country: France
facility: Institut Bergonie
city: Marseille
country: France
facility: Hopital Timone Adultes; Oncologie Medicale Et Usp
city: Montpellier cedex 5
country: France
facility: ICM; Medecine B3
city: Villejuif
country: France
facility: Gustave Roussy Cancer Campus
city: Essen
country: Germany
facility: Universitätsklinikum Essen; Innere Klinik (Tumorforschung)
city: Haifa
country: Israel
facility: Rambam Medical Center; Oncology
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Auckland
country: New Zealand
facility: Auckland City Hospital; Clinical Oncology
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz
city: Moscow
country: Russian Federation
facility: N.N.Burdenko Main Military Clinical Hospital; Oncology Dept
city: Saint-Petersburg
country: Russian Federation
facility: S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
city: Singapore
country: Singapore
facility: National University Hospital; National University Cancer Institute, Singapore (NCIS)
city: Singapore
country: Singapore
facility: National Cancer Centre; Medical Oncology
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital del Mar; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra Madrid; Servicio de Oncología
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Geneve
country: Switzerland
facility: Hôpitaux Universit. de Genève Médecine Oncologie; Oncologie
city: Tainan
country: Taiwan
facility: National Cheng Kung Uni Hospital; Dept of Hematology and Oncology
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; Dept of Oncology
city: Adana
country: Turkey
facility: Adana Baskent University Hospital; Medical Oncology
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty; Medical Oncology Department
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty; Medikal Onkoloji Departmani
city: Izmir
country: Turkey
facility: ?zmir Medical Park; Onkoloji
city: Kadiköy
country: Turkey
facility: Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology
city: London
country: United Kingdom
facility: Barts
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust; Medical Oncology
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital; Institute of Cancer Research
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: