simlukafusp alfa (RG7461) / Roche - LARVOL DELTA

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=341 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

Phase 1b study of immunocytokine simlukafusp alfa (FAP-IL2v) combined with pembrolizumab for treatment of advanced and/or metastatic melanoma (Cancer Res Commun) - P1b | N=83 | NCT03875079 | Sponsor: Hoffmann-La Roche | "Eighty-three patients were treated, 16 patients in two safety run-in cohorts, and 67 patients in two extension cohorts; 75 (90.4%) patients were CPI-experienced. The PK of FAP-IL2v in combination with pembrolizumab was similar to that after administration as monotherapy. Consistent with the proposed mode-of-action, FAP-IL2v preferentially expanded NK and CD8 T cells....A response was observed in 5 of 75 (6.7%) CPI-experienced patients (all partial responses) and in 2 of 8 CPI-naïve patients (one complete, one partial response). The median progression-free survival was 3.1 months."

P1 data • Melanoma

Phase 1b study of immunocytokine simlukafusp alfa (FAP-IL2v) combined with pembrolizumab for treatment of advanced and/or metastatic melanoma. (PubMed, Cancer Res Commun) - P1 | "The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in melanoma patients with prior CPI due to the lack of clinical activity."

Journal • P1 data • Melanoma • Oncology • Solid Tumor • CD8

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=340 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2026 ➔ Jan 2025 | Trial primary completion date: Oct 2025 ➔ Jan 2025

Metastases • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

Phase 1b Study of the Immunocytokine Simlukafusp alfa (FAP-IL2v), in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma. (PubMed, Clin Cancer Res) - P1a/1b | "The safety profile of FAP-IL2v in combination with cetuximab was acceptable and pharmacodynamic markers support the proposed mode-of-action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).]."

Combination therapy • Journal • P1 data • Head and Neck Cancer • Oncology • Renal Disease • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL2RA • ISG20

Phase 1b Study of the Immunocytokine Simlukafusp alfa (FAP-IL2v), in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma (Clin Cancer Res) - P1a/1b | N=134 | NCT02627274 | Sponsor: Hoffmann-La Roche | "A total of 58 patients were enrolled, 19 patients into the dose-escalation, and 39 patients into the expansion part....The most common FAP-IL2v-related adverse events with a grade 3 or 4 severity were hypophosphatemia (19%), lymphopenia (16%), and infusion-related reaction (14%). The pharmacokinetics of FAP-IL2v in combination with cetuximab was similar to that after administration as monotherapy. Consistent with the proposed mode-of-action, FAP-IL2v preferentially expanded intratumoral NK and CD8 T cells. Four patients achieved a partial response, the objective response rate was 7% (95% CI: 3.2, 14.7)."

P1 data • Squamous Cell Carcinoma of Head and Neck

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. (PubMed, EBioMedicine) - P2 | "FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC."

Biomarker • Clinical • Journal • Metastases • P2 data • Preclinical • Retrospective data • Review • Cervical Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • PD-L1

Phase 1 study of simlukafusp alfa (FAP-IL2v) with or without atezolizumab in Japanese patients with advanced solid tumors. (PubMed, Cancer Res Commun) - "This study describes the safety/tolerability of FAP-IL2v 10 mg alone and in combination with atezolizumab in Japanese patients with advanced solid tumors; one DLT (hypotension) occurred with FAP-IL2v 15/20 mg. However, dose escalation of FAP-IL2v was not conducted due to early study termination."

Journal • Metastases • P1 data • Developmental Disorders • Hypotension • Oncology • Solid Tumor

Phase 1 study of simlukafusp alfa (FAP-IL2v) with or without atezolizumab in Japanese patients with advanced solid tumors (Cancer Res Commun) - P1 | N=11 | "All 11 patients experienced adverse events (AEs) during FAP-IL2v treatment. Although most AEs were of mild severity, four treatment-related AEs led to study treatment discontinuation in two patients; one with infusion-related reaction, hypotension, and capillary leak syndrome, and the other with aspartate aminotransferase increased. No AE-related deaths occurred. One DLT (Grade 3 hypotension) occurred in a patient receiving FAP-IL2v 15/20 mg alone. The RD and MTD could not be determined."

P1 data • Solid Tumor

Phase II Study to Determine the Antitumor Activity and Safety of Simlukafusp Alfa (FAP-IL2v) Combined with Atezolizumab in Esophageal Cancer (Clin Cancer Res) - P2 | N=256 | NCT03386721 | Sponsor: Hoffmann-La Roche | "In the response-evaluable population (N = 34), the best confirmed ORR was 20.6% [95% confidence interval (CI), 10.4–36.8], with a complete response seen in 1 patient and partial responses in 6 patients. The disease control rate was 44.1% (complete response = 2.9%; partial response = 17.6%; stable disease = 23.5%), and the median duration of response was 10.1 mon/ths (95% CI, 5.6–26.7). The median progression-free survival was 1.9 months (95% CI, 1.8–3.7). Analysis of response by PDL1 expression (Ventana SP263) resulted in an ORR of 26.7% for patients with PDL1-positive tumors (tumor area positivity cutoff ≥1%; n = 15) and 7.1% for patients with PDL1-negative tumors (tumor area positivity cutoff <1%; n = 14)."

P2 data • Esophageal Cancer

Phase II study to determine the anti-tumor activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in esophageal cancer (Clin Cancer Res) - P2 | N=256 | NCT03386721 | Sponsor: Hoffmann-La Roche | "In the response-evaluable population (N=34), best confirmed ORR was 20.6% (95% confidence interval [CI]: 10.4–36.8) with a complete response (CR) seen in one patient and partial responses (PR) in six patients. Disease control rate was 44.1% (CR=2.9%; PR=17.6%; stable disease [SD]=23.5%) and median duration of response was 10.1 months (95% CI: 5.6–26.7). Median progression-free survival was 1.9 months (95% CI: 1.8–3.7). Analysis of response by PD-L1 expression (Ventana SP263) resulted in an ORR of 26.7 % for patients with PD-L1-positive tumors (tumor area positivity [TAP] cut-off ≥1%; n=15) and 7.1% for patients with PD-L1-negative tumors (TAP cut-off <1%; n=14)."

P2 data • Esophageal Cancer

Phase II study to determine the anti-tumor activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in esophageal cancer. (PubMed, Clin Cancer Res) - P2 | "FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC."

IO biomarker • Journal • P2 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-L1

Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors. (PubMed, Clin Cancer Res) - P1a/1b | "FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors."

Journal • Metastases • P1 data • PK/PD data • Fatigue • Hepatology • Infectious Disease • Liver Failure • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • CD4 • CD8 • IL2 • IL2RA

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=340 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=340 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2024 ➔ Oct 2026 | Trial primary completion date: Jun 2024 ➔ Oct 2025

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

Clinical activity, safety, and PK/PD from a Phase 1 study of RO6874281, a fibroblast activation protein (FAP) targeted interleukin-2 variant (IL-2v) (ESMO 2018) - P1a/1b; "RO6874281 is the first targeted IL-2 variant with acceptable outpatient safety to display monotherapy activity, including in tumor types not previously reported to respond to IL-2. Ph1b/Ph2 studies in combination with atezolizumab and other agents are currently underway."

Clinical • P1 data • PK/PD data • Head and Neck Cancer • Melanoma • Renal Cell Carcinoma

BP40234: Basket Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa as a Combination Therapy in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P2 | N=256 | Terminated | Sponsor: Hoffmann-La Roche | Completed ➔ Terminated; The Sponsor discontinued the development of Simlukafusp alfa due to portfolio prioritization, not due to any safety, efficacy, or quality issues.

Combination therapy • Metastases • Pan tumor • Trial termination • Cervical Cancer • Esophageal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD8

A Study Evaluating Safety, Pharmacokinetics, and Therapeutic Activity of RO6874281 as a Single Agent (Part A) or in Combination With Trastuzumab or Cetuximab (Part B or C) (clinicaltrials.gov) - P1a/1b | N=134 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Breast Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD20

A Study To Evaluate Safety And Therapeutic Activity Of RO6874281 In Combination With Pembrolizumab, In Participants With Advanced Or Metastatic Melanoma (clinicaltrials.gov) - P1 | N=83 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF • CD8 • FAP • FOXP3 • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=290 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

BP40234: Basket Study to Evaluate the Therapeutic Activity of Simlukafusp Alfa as a Combination Therapy in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P2 | N=256 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Combination therapy • Pan tumor • Trial completion • Cervical Cancer • Esophageal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD8

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=290 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2022 ➔ Jun 2024 | Trial primary completion date: Nov 2022 ➔ Jun 2024

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

A Study Evaluating Safety, Pharmacokinetics, and Therapeutic Activity of RO6874281 as a Single Agent (Part A) or in Combination With Trastuzumab or Cetuximab (Part B or C) (clinicaltrials.gov) - P1a/1b; N=134; Active, not recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2021 ➔ Dec 2022

Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD20

[VIRTUAL] Simlukafusp α and cetuximab combination in patients with recurrent, unresectable or metastatic squamous cell carcinoma of the head and neck (ESMO 2021) - P1a/1b | "The safety profile of SIM in combination with CET was consistent with the safety of each component, and did not lead to unexpected overlapping toxicities. Despite exceptional responders with prior CPI, overall low anti-tumor activity does not warrant further clinical exploration in HNSCC."

Clinical • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • FAP • IL2