cibisatamab (RG7802) / Roche - LARVOL DELTA

CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials. (PubMed, Nat Commun) - P1 | "Cibisatamab is a bispecific antibody-based construct targeting carcinoembryonic antigen (CEA) on tumour cells and CD3 epsilon chain as a T-cell engager. ADA appearance could be mitigated by obinutuzumab-pretreatment, with 8% of patients having persistent ADAs. Overall, cibisatamab warrants further exploration in immunotherapy combination strategies for MSS-CRC."

Journal • P1 data • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CEACAM5

FAP-targeted 4-1BBL trimeric costimulation amplifies T-cell activation and antitumor efficacy of a CEA-directed T-cell engager in MSS colorectal cancer (AACR 2026) - P1 | "Full T-cell activation, however, requires integrated signaling through the TCR-CD3 complex and costimulatory pathways such as those mediated by the 4-1BB receptor, expressed on antigen-primed T cells. We evaluated the combination of cibisatamab with escalating doses of FAP-4-1BBL, a fibroblast activation protein (FAP)-dependent 4-1BB agonist, in an open-label Phase 1b study (BP42675; NCT04826003) in patients with MSS mCRC who had progressed after ≥2 prior lines of therapy. The combination of cibisatamab and FAP-4-1BBL demonstrated a manageable safety profile. These data suggest that FAP-targeted 4-1BB costimulation can potentiate the antitumor activity of CEA-directed T-cell bispecific antibodies. The results support further development of tumor-localized 4-1BB agonists in combination with T-cell-engaging therapies for MSS mCRC and other non-inflamed ("cold") tumors."

Clinical • Colorectal Cancer • Oncology • Solid Tumor • CCR7 • CD8 • CEACAM5 • PD-1 • TNFRSF9

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=314 | Terminated | Sponsor: Hoffmann-La Roche | Completed ➔ Terminated; Study was closed early as the sponsor decided not to continue development of certain treatment combinations.

Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers. (PubMed, Oncol Res) - "We summarize key molecular targets and highlight representative clinical candidates such as CEA-TCB and RG7802...We conclude by outlining future research directions and emphasizing the importance of interdisciplinary, multicenter collaborations to accelerate clinical translation and maximize the therapeutic potential of BsAbs in GI oncology. In summary, the aim of this study is to critically evaluate the current landscape of BsAb-based immunotherapy in gastrointestinal cancers, synthesizing emerging molecular targets, evaluating clinical trial outcomes, identifying key challenges limiting therapeutic efficacy, and proposing evidence-based strategies to optimize future BsAb development."

IO biomarker • Journal • Review • Gastrointestinal Cancer • Liver Cancer • Oncology • Solid Tumor

Cibisatamab and FAP-4-1BBL in microsatellite-stable colorectal cancer: a phase 1b trial. (PubMed, Nat Med) - P1 | "Patients received cibisatamab with escalating doses of FAP-4-1BBL weekly or every 3 weeks after obinutuzumab pretreatment to mitigate anti-drug antibody formation. These findings demonstrate the feasibility of combining tumor antigen-directed T cell engagement with localized co-stimulation, with evidence of immune activation and preliminary antitumor activity supporting further clinical development. ClinicalTrials.gov identifier: NCT04826003 ."

IO biomarker • Journal • P1 data • Colorectal Cancer • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • Solid Tumor • CD8 • CEACAM5 • IFNG • IL2RA • TNFRSF9

Cibisatamab and FAP-4-1BBL in microsatellite-stable colorectal cancer: a phase 1b trial (Nature) - "Among 52 treated patients, the combination showed a manageable safety profile. Dose-limiting toxicities occurred in 2 out of 52 patients (3.8%). Cytokine release syndrome (CRS) occurred in 30 out of 52 patients (57.7%; grade ≥3: 2 out of 52, 3.8%) and was manageable; after a cycle 1 cibisatamab dose reduction to 60 mg, serious CRS occurred in 4 out of 27 patients (14.8%; grade ≥3: 0 out of 27)....Confirmed partial responses were observed in 7 out of 52 patients (13.5%). Pharmacodynamic analyses demonstrated systemic immune activation, including increased IFNγ, soluble CD25, soluble 4-1BB (CD137) and activated, proliferating CD8+ T cells."

P1 data • Colorectal Cancer

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: Hoffmann-La Roche | N=410 ➔ 250

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=314 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=675 ➔ 314

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=314 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=410 | Recruiting | Sponsor: Hoffmann-La Roche | N=292 ➔ 410

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=307 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=435 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Feb 2024 ➔ Nov 2023

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=380 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Apr 2022 ➔ Nov 2023

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=675 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Jun 2026 ➔ Sep 2025 | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2027 ➔ Nov 2026

Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=470 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2025 ➔ Nov 2026 | Trial primary completion date: Apr 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=675 | Recruiting | Sponsor: Hoffmann-La Roche | N=470 ➔ 675 | Trial completion date: Nov 2026 ➔ Sep 2027 | Trial primary completion date: Aug 2025 ➔ Jun 2026

Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=314 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2026 ➔ Nov 2025

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=435 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2023 ➔ Feb 2024 | Trial primary completion date: Feb 2022 ➔ Jun 2022

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=435 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2023 ➔ Aug 2025 | Trial primary completion date: Feb 2022 ➔ Apr 2024

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov) - P1/2 | N=307 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1/2 trial • Non Small Cell Lung Cancer • PD-L1

CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB. (PubMed, Antibodies (Basel)) - "For the assessment of the combination of CEA-TCB with CEA-4-1BBL, co-stimulatory antibody fusion protein in vitro assays are not sufficient to fully capture the complex relationships affecting efficacy. Thus, screening with different cell assays and in vivo efficacy studies in combination with CEA-TCB are essential to select the best candidate. Based on the totality of data on the T84.66-LCHA-4-1BBL antibody fusion protein comprising the CEACAM5 antibody, T84.66-LCHA was selected as the optimal combination partner for CEA-TCB."

Journal • Oncology • CEACAM5

BP42675: Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290 In Combination With Cibisatamab With Obinutuzumab Pre-Treatment (clinicaltrials.gov) - P1 | N=54 | Completed | Sponsor: Hoffmann-La Roche | Phase classification: P1/2 ➔ P1

Phase classification • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • CEACAM5 • CSF2

A Model-Based Approach to Evaluate Anti-Drug Antibody Impact on Drug Exposure With Biologics: A Case Example With the CD3 T-Cell Bispecific Cibisatamab. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The administration of biologics can lead to immunogenic responses that trigger anti-drug antibody (ADA) formation. The investigated patient demographics, dose or dosing schedule, or atezolizumab coadministration were not identified as factors influencing exposure loss due to ADAs. The developed model can be used to differentiate patients with and without ADA-driven exposure loss, as well as for a precise PK characterization in patients even with ADA formation."

Journal • Oncology

In Vitro Evaluation of the Safety and Efficacy of Cibisatamab Using Adult Stem Cell-Derived Organoids and Colorectal Cancer Spheroids. (PubMed, Cancers (Basel)) - "This highlights our model's potential to predict clinical immunotherapy outcomes, capturing complex responses like immune activation, therapeutic selectivity, and potential resistance mechanisms. These findings underscore the utility of our model as a reliable, physiologically relevant tool for screening new immunotherapies and advancing our understanding of tumor-immune dynamics."

IO biomarker • Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • CEACAM5 • GZMB

BP42675: Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290 In Combination With Cibisatamab With Obinutuzumab Pre-Treatment (clinicaltrials.gov) - P1/2 | N=54 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | N=80 ➔ 54

Enrollment change • Trial completion • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • CEACAM5