Raludotatug deruxtecan (R-DXd; DS-6000) a CDH6-directed antibody-drug conjugate (ADC) appears to be safe and produced early evidence of clinical response in patients with heavily pretreated, platinum-resistant ovarian cancer in an initial phase 1 clinical trial (NCT04707248).1
About Platinum Resistant Ovarian Cancer
Each year in the United States, approximately 22,000 women are diagnosed with ovarian cancer, and it is the fifth most common cause of cancer-related deaths among women. Ovarian cancer is considered to be platinum resistant when the cancer either fails to respond to treatment with platinum based chemotherapy or recurs relatively quickly following chemotherapy treatment.
Antibody-drug conjugates (ADC) and Bispecific antibody constructs represent the most recent type of precision cancer medicines being developed for the treatment of cancer including patients with ovarian cancer. Antibody-drug-conjugates work by delivering cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on the lung cancer cells.
Elahere (mirvetuximab) was the first ADC approved for the treatment of ovarian cancer. Elahere targets the folate receptor alpha (FRα) on cancer cells and delivers anti-cancer tubulin-targeting DM4 directly to the cell.
About Raludotatug deruxtecan (R-DXd)
Over expression of the cell adhesion protein CDH6 occurs in approximately 65% to 85% of patients with ovarian cancer and is associated with a poor prognosis. R-DXd consists of a humanized anti-CDH6 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload. Monoclonal antibody delivers the cancer killing payload to cells expressing CDH6 and is being tested in ovarian cancer.
At doses ranging from 4.8 mg/kg to 8.0 mg/kg 23 of 50 (46% ) of individuals with platinum resistant ovarian cancer experienced a response to treatment with R-Dxd including 1 complete response. The median time to response was 6 weeks and the median duration of response was 11.2 months. Pre-testing for CDH6 positivity was not required for participation in the study.
Treatment was generally well tolerated however 3.3% of individuals developed severe interstitial lung disease (ILD) at the higher 8.0 mg/kg dose being evaluated. ILD is a known significant side effect of many ADC’s that requires early identification, treatment and cessation of ADC therapy.
Assessment will continue at the remaining 3 dose levels, and a late-phase study further evaluating R-DXd in patients with ovarian cancer is forthcoming.
How do test for CDH6?
Testing can be performed by immunohistochemistry on the cancer tissue that was stored from the initial biopsy and/or surgery. Currently there is not a blood test available for testing.
Connect With Others for Support and information
CancerConnect was the first social network created for people with ovarian cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed CancerConnect programs since 1997. CancerConnect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating cancer from others. Share your experience, ask a question, or start a conversation by posting on CancerConnect.
References
- Moore K, Philipovskiy A, Harano K, et al. Raludotatug deruxtecan (R-DXd; DS-6000) monotherapy in patients with previously treated ovarian cancer (OVC): subgroup analysis of a first-in-human phase I study. Ann Oncol. 2023;34(suppl 2):S510. doi:10.1016/j.annonc.2023.09.1924
- FDA grants accelerated approval to mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer. News release. FDA. November 14, 2022. Accessed November 16, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant
