RG7827

P1, N=54, Completed, Hoffmann-La Roche | Phase classification: P1/2 --> P1

P1/2, N=272, Active, not recruiting, Hoffmann-La Roche | Trial completion date: May 2026 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

Increased FAP expression in the TME as a result of radiotherapy can be exploited to target agonist 4-1BB immunotherapy to malignant tumor lesions using an FAP-4-1BBL antibody fusion protein.

P1/2, N=54, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | N=80 --> 54

P1/2, N=272, Active, not recruiting, Hoffmann-La Roche | N=645 --> 272

In this work, a workflow to select binding affinities for bispecific antibodies that integrates preclinical in vitro data, mathematical modeling and simulation, and knowledge on target expression in the patient population, is provided. The early implementation of this approach can increase the probability of success with cancer immunotherapy in clinical development.

P1/2, N=645, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> May 2026

P1/2, N=80, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jul 2025 --> Dec 2024 | Trial primary completion date: Jul 2025 --> Dec 2024

P1/2, N=80, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

We integrated in vitro data with mathematical modeling to characterize the pharmacology of FAP-4-1BBL as a function of trimeric complex formation when combined with the T-cell engager cibisatamab. Depending on the dosing schedule and FAP-4-1BBL plasma: tumor distribution, doses between 2 and 145 mg could lead to maximum trimeric complex formation in the clinic. Due to the expected variability in both pharmacokinetic and FAP expression in the patient population, we predict that detecting a clear dose-response relationship would remain difficult without a large number of patients per dose level, highlighting that mathematical modeling techniques based on in vitro data could aid dose selection.

Findings from a phase I study of the bispecific antibody RO7122290, which targets CD137 and the fibroblast activity protein, show that it produces responses in patients with advanced solid tumors-without the liver toxicity associated with earlier therapies targeting CD137. Additional research evaluating RO7122290 in combination with atezolizumab or other immune agents is planned.

Eleven patients experienced a complete or partial response, six of whom were confirmed to be immune checkpoint inhibitor naive. These results support further evaluation of RO7122290 in combination with atezolizumab or other immune-oncology agents for the treatment of solid tumors.