MP0310 / Molecular Partners, BeOne Medicines - LARVOL DELTA

Improvement of daratumumab- or elotuzumab-mediated NK cell activity by the bi-specific 4-1BB agonist, DARPin α-FAPx4-1BB: A preclinical study in multiple myeloma. (PubMed, Biomed Pharmacother) - "In their BM niche, MM cells adhere to FBs sustaining immune evasion, drug resistance and the undetectable endurance of tumor cells known as minimal residual disease (MRD). Here, we describe the novel bi-specific designed ankyrin repeat protein (DARPin) α-FAPx4-1BB (MP0310) with FAP-dependent 4-1BB agonistic activity. Therefore, α-FAPx4-1BB enhanced both the adhesion of daratumumab-treated NK cells on FBs as well as their activation by improving release of CD107a and perforin, hence MM cell killing via antibody-mediated cell cytotoxicity (ADCC). Interestingly, α-FAPx4-1BB significantly potentiated daratumumab-mediated ADCC in the presence of FBs, suggesting that it may overcome the BM FBs' immunosuppressive effect. Overall, we speculate that treatment with α-FAPx4-1BB may represent a valuable strategy to improve mAb-induced NK cell activity fostering MRD negativity in MM patients through the eradication of latent MRD cells."

Journal • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • LAMP1

Study to Investigate the Safety, Blood Levels and Activity of MP0310 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=38 | Completed | Sponsor: Molecular Partners AG | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

Study to Investigate the Safety, Blood Levels and Activity of MP0310 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=38 | Active, not recruiting | Sponsor: Molecular Partners AG | Recruiting ➔ Active, not recruiting | N=58 ➔ 38

Enrollment change • Enrollment closed • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

MOLECULAR PARTNERS TO REGAIN GLOBAL RIGHTS FOR MP0310 FROM AMGEN (Molecular Partners Press Release) - "Molecular Partners AG...announced that Amgen, its collaboration partner for MP0310 (AMG 506), has informed the Company of their decision to return global rights of MP0310 to Molecular Partners following a strategic pipeline review. Molecular Partners is presently conducting a phase 1 study of MP0310 and will look to present full phase 1 data at a scientific conference when available....Data from the second part of the trial is pending. The remaining patient cohorts will be treated and followed, per the trial protocol, which is expected to be completed in the second half of 2022."

Licensing / partnership • Trial status • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Study to Investigate the Safety, Blood Levels and Activity of MP0310 (AMG 506) in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=58; Recruiting; Sponsor: Molecular Partners AG; Trial primary completion date: Oct 2021 ➔ Jul 2022

Clinical • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

Molecular Partners Highlights Upcoming Oncology Portfolio Presentations in December (GlobeNewswire) - "Molecular Partners AG...announced a series of events in December 2021 that will highlight various aspects of its DARPin cancer therapeutic portfolio. These events include a presentation at the European Society of Medical Oncology Immuno-Oncology (ESMO-IO) Congress, focused on the clinical-stage fibroblast activation protein (FAP)-targeted CD40 activator candidate, MP0317; a presentation at the American Society of Hematology (ASH) Annual Meeting, focused on MP0533, the company’s acute myeloid leukemia (AML) candidate...and a comprehensive review of the company’s cancer portfolio and its research & development strategy at a virtual Oncology Day to be held at 8:30 am ET on December 15, 2021....Clinical development of MP0533 is expected to initiate in 2022."

New trial • P1 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Study to Investigate the Safety, Blood Levels and Activity of MP0310 (AMG 506) in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=58; Recruiting; Sponsor: Molecular Partners AG; Trial completion date: Apr 2023 ➔ Dec 2022; Trial primary completion date: Apr 2021 ➔ Oct 2021

Clinical • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI

[VIRTUAL] Selection of first-in-human clinical dose range for the tumor-targeted 4-1BB agonist MP0310 (AMG 506) using a pharmacokinetic/pharmacodynamics modeling approach (AACR-II 2020) - "It provides a rationale for selecting the maximum tested dose, and may help reduce the number of cancer patients receiving sub-therapeutic doses. MP0310 (AMG 506) is currently being evaluated in a Ph1 clinical study."

Clinical • P1 data • PK/PD data • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • FAP • TNFA

Molecular Partners to present preclinical data from MP0317, AMG 506 / MP0310 and peptide-MHC programs at AACR Annual Meeting (Molecular Partners Press Release) - "Thirdly, a poster to be presented on AMG 506 / MP0310 (FAP x 4-1BB) describes pharmacokinetic and pharmacodynamic research to establish the optimal dose range for this novel tumor-localized immune agonist. AMG 506 / MP0310 is now in a Phase 1 clinical study."

Preclinical • Oncology

Molecular Partners announces first patient dosed in phase 1 trial of MP0310, a novel tumor-localized immunotherapy (Yahoo Finance) - “Molecular Partners AG…announced that the first patient has been enrolled and dosed in a Phase 1 first-in-human study of MP0310 as a single agent in patients with advanced solid tumors….MP0310-CP101 intends to enroll up to 54 patients at three sites in France.”

Enrollment open

Study to Investigate the Safety, Blood Levels and Activity of MP0310 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=54; Recruiting; Sponsor: Molecular Partners AG; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Study to Investigate the Safety, Blood Levels and Activity of MP0310 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=54; Not yet recruiting; Sponsor: Molecular Partners AG

Clinical • New P1 trial