RG7882 / Roche, Pfizer - LARVOL DELTA

Preclinical assessment of HWK-016, a next-generation, MUC16-targeting ADC with novel bioconjugation and linker-payload technology (AACR 2026) - "Early clinical trials of MUC16-targeted ADCs, DMUC5754A and DMUC4064A, showed promising efficacy but were limited by targeting an epitope within the shed extracellular domain (ECD) of MUC16, leading to off-target binding to circulating CA125, which created an antigen sink. In summary, HWK-016 is a highly potent, MUC16-targeted ADC directed to the MUC16 non-shed ECD to avoid circulating CA125 binding. A phase I dose-escalation study is planned to evaluate HWK-016 in patients with advanced malignant solid tumors."

ADC • IO biomarker • Preclinical • Lung Cancer • Oncology • Solid Tumor • MUC16 • MUC4

Therapeutic Applications and Target Strategies of Antibody-Drug Conjugates in Ovarian Cancer. (PubMed, Iran J Pharm Res) - "This review summarizes a range of ADCs targeting tumor-associated antigens in ovarian cancer, including mirvetuximab soravtansine (MIRV), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), sacituzumab tirumotecan (SKB-264), PF-06664178, anetumab ravtansine (BAY 94-9343), BMS-986148, DMOT4039A, RC88, lifastuzumab vedotin (DNIB0600A), upifitamab rilsodotin (ABBV-181), ZW220, DMUC4064A, and sofituzumab vedotin (DMUC5754A). The ADCs hold significant potential to reshape the treatment landscape for ovarian cancer by providing targeted therapeutic options. Further research is required to optimize patient selection, address resistance mechanisms, and improve safety profiles."

Journal • Review • Oncology • Ovarian Cancer • Solid Tumor • MUC4

Pharmacokinetics of a THIOMABTM antibody drug conjugate (TDC): DMUC4064A in a phase 1 study with platinum-resistant ovarian cancer (AACR 2017) - "Compared to the conventional anti-MUC16 ADC (DMUC5754A, DAR 3.5) at 2.4 mg/kg (MTD), the TDC DMUC4604A at 5.6 mg/kg demonstrates a greater than 3 fold slower acMMAE clearance1. In this ongoing study of DMUC4604A, nonlinear PK of acMMAE and tAb were observed over the dose range studied, and exposures of acMMAE and tAb were highly correlated. This is the first report of clinical PK data of a TDC demonstrating slower clearance compared to a conventional ADC format."

Clinical • P1 data • Biosimilar • Gynecologic Cancers • Oncology • Ovarian Cancer

Targeting MUC16 with the THIOMABTM-drug conjugate DMUC4064A in patients with platinum-resistant ovarian cancer: a Phase I escalation study (AACR 2017) - P1; "These data are the first reported for an MMAE-containing TDC in a clinical trial (clinicaltrials.gov NCT02146313). DMUC4064A has an acceptable safety profile with improved stability compared to MUC16 MMAE ADC and shows evidence of anti-tumor activity, warranting further evaluation in ovarian cancer."

Clinical • P1 data • Biosimilar • Breast Cancer • Cardiovascular • Dry Eye Disease • Gynecologic Cancers • Heart Failure • Immunology • Ocular Inflammation • Oncology • Ophthalmology • Ovarian Cancer • Pain

An open-label phase I dose-escalation study of the safety and pharmacokinetics of DMUC4064A in patients with platinum-resistant ovarian cancer. (PubMed, Gynecol Oncol) - "In this Phase I study, DMUC4064A demonstrated a tolerable safety profile along with encouraging efficacy in the indication of platinum-resistant OC."

Clinical • Journal • P1 data • PK/PD data • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Oncology • Ovarian Cancer • Pain • Solid Tumor • MUC16 • MUC4

Targeting MUC16 with the THIOMABTM-drug conjugate DMUC4064A in patients with platinum-resistant ovarian cancer: A phase I expansion study (AACR 2018) - P1; "Treatment with DMUC4064A (clinicaltrials.gov NCT02146313) at 5.2 mg/kg has an acceptable safety profile in PROC, a patient population with few treatment options. The ocular toxicities with DMUC4064A appear manageable and the overall and depth of response demonstrate promising anti-tumor activity."

Clinical • P1 data • Ovarian Cancer

A Study Evaluating the Safety and Pharmacokinetics of DMUC4064A in Participants With Platinum-Resistant Ovarian Cancer or Unresectable Pancreatic Cancer (clinicaltrials.gov) - P1; N=100; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting; N=75 ➔ 100

Enrollment change • Enrollment closed • Biosimilar • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor