Clinical trial · Interventional
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): The Sponsor discontinued the development of Simlukafusp alfa due to portfolio prioritization, not due to any safety, efficacy, or quality issues.
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced/Metastatic Head and Neck, Oesophageal and Cervical Cancers | — | UNRESOLVED | — |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody | Drug | — | UNRESOLVED |
| Gemcitabine | Drug | Gemcitabine | ALIAS |
| simlukafusp alfa | Drug | — | UNRESOLVED |
| Vinorelbine | Drug | Vinorelbine | ALIAS |
Design
Arms and outcomes
Arms (17)
- type
- EXPERIMENTAL
- label
- Cohort A (Part I)
- 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.
- interventionNames
- Drug: simlukafusp alfa
- Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
- type
- EXPERIMENTAL
- label
- Cohort B (Part I)
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (2)
- DERIVEDVerlingue L, Italiano A, Prenen H, Guerra Alia EM, Tosi D, Perets R, Lugowska I, Moiseyenko V, Gumus M, Arslan C, Lindsay CR, Deva S, Taus A, Oaknin A, Rottey S, Cicin I, Goksu SS, Smolin A, Rosello-Keranen S, Habigt C, Marbach D, Boetsch C, Dejardin D, Sleiman N, Evers S, Richard M, Ardeshir C, Charo J, Kraxner A, Teichgraber V, Keshelava N, Dziadziuszko R. Phase 2 study of the antitumour activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in patients with recurrent and/or metastatic cervical squamous cell carcinoma. EBioMedicine. 2024 Nov;109:105374. doi: 10.1016/j.ebiom.2024.105374. Epub 2024 Oct 11. PMID 39395231
- DERIVEDPrenen H, Deva S, Keam B, Lindsay CR, Lugowska I, Yang JC, Longo F, de Miguel M, Ponz-Sarvise M, Ahn MJ, Gumus M, Champiat S, Italiano A, Salas S, Perets R, Arslan C, Cho BC, Evers S, Boetsch C, Marbach D, Dejardin D, Sleiman N, Ardeshir C, Richard M, Charo J, Kraxner A, Keshelava N, Teichgraber V, Moreno V. Phase II Study to Determine the Antitumor Activity and Safety of Simlukafusp Alfa (FAP-IL2v) Combined with Atezolizumab in Esophageal Cancer. Clin Cancer Res. 2024 Jul 15;30(14):2945-2953. doi: 10.1158/1078-0432.CCR-23-2677. PMID 38709220