eciskafusp alfa (RG6279) / Roche - LARVOL DELTA

A Study to Evaluate Eciskafusp Alfa in Combination With Bacillus Calmette-guerin (BCG) in Participants With BCG-unresponsive High-risk Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Hoffmann-La Roche | N=110 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • IO biomarker • Trial withdrawal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PD-L1

A Study to Evaluate Safety and Anti-Tumor Activity of Eciskafusp Alfa (RO7284755) Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=189 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2027 ➔ Aug 2026 | Trial primary completion date: Nov 2026 ➔ Jan 2026

IO biomarker • Trial completion date • Trial primary completion date • Tumor mutational burden • Oncology • Solid Tumor • PD-L1

A Study to Evaluate Eciskafusp Alfa in Combination With Bacillus Calmette-guerin (BCG) in Participants With BCG-unresponsive High-risk Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PD-L1

A Study to Evaluate Eciskafusp Alfa in Combination With Bacillus Calmette-guerin (BCG) in Participants With BCG-unresponsive High-risk Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P1 | N=110 | Not yet recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P1/2 ➔ P1

Phase classification • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A Study to Evaluate Eciskafusp Alfa in Combination With Bacillus Calmette-guerin (BCG) in Participants With BCG-unresponsive High-risk Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P1/2 | N=110 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1/2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A Study to Evaluate Safety and Anti-Tumor Activity of Eciskafusp Alfa (RO7284755) Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=189 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Oncology • Solid Tumor

Preclinical characterization of MBS309, a conditionally active PD-1-dependent IL-2 mutation with significantly superior anti-tumor efficacy with safety (AACR 2024) - "In our in vivo tumor murine models, 1mg/kg MBS309 showed much better suppression effect in MC38/hPD-L1 tumor than 1mg/kg RG6279 analog and Pembrolizumab (1mg/kg) combination with wild type IL-2 (0.1mg/kg); And MBS309 at the dosage of 5mg/kg can significantly inhibit tumor growth in PD-1 resistant Pan-02 xenograft models without any side-effects observed, while RG6279 analog at the dosage of 5mg/kg induced severe body reduction of the mice and resulted in 80% (4/5) mice death after two dosages...20mg/kg of MBS309 was well tolerated in mouse, while 10mg/kg of RG6279 analog or PF-07209960 analog show severe toxicity and resulted in death of all the mice...And it shows much higher anti-tumor effect compared to anti-PD-1/-L1 antibodies alone in both PD-1 sensitive and resistant tumor models. MBS309 has demonstrated a favorable safety profile and highly anti-tumor activities in vivo, which has the potential to supporting its clinical development for the treatment of cancer."

IO biomarker • Preclinical • Oncology • CD8 • IL2 • PD-1

A Study to Evaluate Safety and Anti-Tumor Activity of Eciskafusp Alfa (RO7284755) Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=256 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P1a/1b ➔ P1 | Trial completion date: Nov 2026 ➔ May 2027 | Trial primary completion date: May 2026 ➔ Nov 2026

Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Beyond checkpoint inhibition: PD-1 cis-targeting of an IL-2Rβγ-biased interleukin-2 variant as a novel approach to build on checkpoint inhibition. (PubMed, Oncoimmunology) - "The immunocytokine PD1-IL2v was designed to overcome liabilities and improve efficacy of IL-2 therapies. PD1-IL2v preferentially targets PD-1 T-cells and acts on antigen-specific stem-like PD-1 TCF-1 CD8 T-cells expanding and differentiating them towards better effectors resulting in superior efficacy in LCMV chronic infection and tumor models compared to checkpoint inhibition."

Checkpoint inhibition • Journal • Infectious Disease • Oncology • IL2

A Study to Evaluate Safety and Anti-Tumor Activity of RO7284755 Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1a/1b | N=348 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2027 ➔ Nov 2026 | Trial primary completion date: Mar 2027 ➔ May 2026

Combination therapy • IO biomarker • Metastases • Trial completion date • Trial primary completion date • Tumor mutational burden • Oncology • Solid Tumor • CD8 • PD-1 • PD-L1 • TCF7 • TMB

A Study to Evaluate Safety and Anti-Tumor Activity of RO7284755 Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1a/1b | N=440 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2024 ➔ Jun 2027 | Trial primary completion date: Apr 2024 ➔ Mar 2027

Combination therapy • IO biomarker • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • CD8 • PD-1 • PD-L1 • TMB

A Study to Evaluate Safety and Anti-Tumor Activity of RO7284755 Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1a/1b; N=440; Not yet recruiting; Sponsor: Hoffmann-La Roche

Clinical • Combination therapy • IO biomarker • New P1 trial • Oncology • Solid Tumor • CD8 • PD-L1 • TMB

A Study to Evaluate Safety and Anti-Tumor Activity of RO7284755 Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1a/1b; N=440; Recruiting; Sponsor: Hoffmann-La Roche; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • IO biomarker • Oncology • Solid Tumor

[VIRTUAL] PD1-IL2v: A next generation, PD-1-targeted cytokine (AACR 2021) - "High-affinity PD-1 binding allows IL2v to effectively expand tumor-antigen specific T-cells, and to differentiate those cells towards better, non-dysfunctional immune effectors, to much higher levels vs. anti-PD-1/-L1 antibodies alone or in combination with either tolerable doses of standard IL-2 or with a non-PD-1-targeted 2nd generation IL-2Rbg agonist currently in clinical development, and thus mediate significantly superior anti-tumor efficacy at well tolerated drug doses. PD1-IL2v is currently being tested in a Ph1 clinical trial."

Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • IL15 • IL2RA

[VIRTUAL] The immunocytokine PD1-IL2v overcomes immune checkpoint resistance, and combination with an anti-PD-L1 antibody further enhances its anti-tumor activity (AACR 2021) - "Notably, we identified up-regulation of PD-L1 on the tumor vasculature in relapsing tumors as a potential factor in the observed adaptive resistance, which encouraged combining an anti-PD-L1 antibody with PD1-IL2v, leading to enhanced therapeutic benefit. The data obtained in this spontaneous de novo tumor model motivate consideration of evaluating the PD1-IL2v/anti-PD-L1 combination therapy in the clinical setting, in particular in anti-PD-1/anti-PD-L1 resistant tumors infiltrated with PD1+CD8+ T cells."

Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • IL2RA • PD-1 • RIPK1

[VIRTUAL] PBMC-based cancer vaccines generated with microfluidics squeezing demonstrate synergistic and durable tumor reduction in combination with PD1 checkpoint and FAP targeted IL-2 variants (SITC 2020) - "Monotherapy with SQZ-PBMC-HPV is currently under clinical evaluation for HPV16+ tumor indications. These preclinical data support the combination of SQZ-PBMC with FAP-IL2v or PD1-IL2v targeted immunocytokine as promising cancer immunotherapies."

Combination therapy • Oncology • CD8 • FAP • IFNG • IL2 • IL2RA • TNFA

[VIRTUAL] PBMC-based cancer vaccines generated with microfluidics squeezing demonstrate synergistic and durable tumor reduction in combination with PD1 checkpoint and FAP targeted IL-2 variants (SITC 2020) - "Monotherapy with SQZ-PBMC-HPV is currently under clinical evaluation for HPV16+ tumor indications. These preclinical data support the combination of SQZ-PBMC with FAP-IL2v or PD1-IL2v targeted immunocytokine as promising cancer immunotherapies."

Combination therapy • Oncology • CD8 • FAP • IFNG • IL2 • IL2RA • TNFA

[VIRTURL] PD1-IL2v: A Next Generation, PD-1-targeted IL-2R Agonist for Cancer Immunotherapy (SITC 2020) - No abstract available

Oncology • IL2RA

Novel immune-cell targeted IL2v to deliver IL-2R signaling to tumor reactive T cells via PD-1 whilst blocking the PD-1 pathway (SITC 2019) - "PD1-IL2v is a differentiated immune cell-targeted IL-2v which promotes an effective and long-term anti-tumor immune-response by delivering IL-2v to PD-1+ tumor-specific T cells"

IO Biomarker • PD(L)-1 Biomarker