ABBV-428 / AbbVie - LARVOL DELTA

Phase I study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumours (ESMO 2019) - P1; "Targeting the tumor microenvironment with ABBV-428 was successful in achieving immune agonism without systemic toxicity in MSLN-expressing advanced solid tumors; however, no significant clinical benefit was observed. Potential mechanisms and additional biomarker/translational findings related to these observations will be presented. Clinical trial identification: NCT02955251."

Clinical • IO biomarker • P1 data • PK/PD data • Oncology • Solid Tumor

[VIRTUAL] Pharmacodynamics and potential predictive biomarkers of ABBV-428, a first-in-class mesothelin (MSLN)-CD40 bispecific, in patients with advanced solid tumors (AACR-I 2020) - P1 | "These data show that ABBV-428 binds and activates CD40 in the blood leading to B cell activation with no evidence of systemic cytokine production or significant change in the tumor immune microenvironment. Evidence of inflamed immune tumor microenvironment was observed at baseline from long-term SD patients. These results may explain the clinical observations from the current ABBV-428 clinical trial."

Biomarker • Clinical • IO Biomarker • PK/PD data • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • Thoracic Cancer • BAP1 • CD40 • CXCL8 • GS • IFNG • IL10 • IL1B • IL2 • IL6 • MSLN • PD-L1

Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors. (PubMed, J Immunother Cancer) - P1 | "ABBV-428 monotherapy exhibited dose-proportional pharmacokinetics and an acceptable safety profile, particularly for toxicities characteristic of CD40 agonism, illustrating that utilization of a tumor-targeted, bispecific antibody can improve the safety of CD40 agonism as a therapeutic approach. ABBV-428 monotherapy had minimal clinical activity in dose escalation and in a small expansion cohort of patients with advanced mesothelioma or ovarian cancer."

Clinical • IO biomarker • Journal • P1 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Immune Modulation • Immunology • Inflammation • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Respiratory Diseases • Solid Tumor

A BISPECIFIC MOLECULE TARGETING CD40 AND TUMOR ANTIGEN MESOTHELIN ENHANCES TUMOR-SPECIFIC IMMUNITY. (PubMed, Cancer Immunol Res) - "Although expression of cell surface mesothelin is necessary, the bispecific molecules induced immune-mediated antitumor activity against both mesothelin+ and mesothelin- tumor cells. ABBV-428 represents a class of bispecific molecules with conditional activity dependent on the binding of a tumor specific antigen, and such activity could potentially maximize antitumor potency while limiting systemic toxicity in clinical studies."

IO Biomarker • Journal • Immune Modulation • Inflammation • Oncology

A Study of ABBV-428, an Immunotherapy, in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=61; Completed; Sponsor: AbbVie; Trial primary completion date: Jul 2019 ➔ Oct 2019

Clinical • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

"perhaps for part 2 but I also had AMG 509 (STEAP1 x CD3 2+1 BiTE) & ABBV 428 (mesothelin x CD40) in the list of new stuff, both preclinical I guess" (@BertrandBio)

Preclinical • CD40 • MSLN

A Study of ABBV-428, an Immunotherapy, in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=61; Completed; Sponsor: AbbVie; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study of ABBV-428, an Immunotherapy, in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=61; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting; N=172 ➔ 61; Trial completion date: Dec 2020 ➔ Oct 2019

Clinical • Enrollment change • Enrollment closed • Trial completion date

A Study of ABBV-428, an Immunotherapy, in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=172; Recruiting; Sponsor: AbbVie; Trial primary completion date: Apr 2019 ➔ Aug 2019

Clinical • Trial primary completion date