The past several years have brought about a revival in the development of a complex, but powerful type of cancer treatment. Known as antibody-drug conjugates, or ADCs, these therapies have newly become a must-have asset for pharmaceutical companies serious about oncology research — a shift from much of the past two decades.
That interest and investment will be on display next month at the annual meeting of the American Society of Clinical Oncology, which will feature scores of presentations on studies testing ADCs in various cancer types.
Abstracts summarizing results from many of those trials were published online Thursday, including for closely watched early studies of experimental ADCs from Merck & Co., Daiichi Sankyo and BioNTech. (Others are being held for release during the meeting.)
For Merck and BioNTech, the conference follows shortly after the companies licensed new ADC candidates in separate deals with, respectively, China-based Kelun Biotech and Duality Biologics. The abstracts disclosed Thursday give investors and analysts watching the companies a better look at why the drugmakers struck a deal.
Merck’s new drug, dubbed SKB264, targets a protein known as TROP2 that’s often overexpressed in non-small cell lung cancer, a common form of the disease. As an ADC, the drug consists of an antibody targeting TROP2 joined via a linking molecule to a toxic derivative of the chemotherapy belotecan.
Study data included in the abstract show that SKB264 shrank tumors in 44% of the 39 participants with advanced lung cancer who were evaluable for a response. Responses were recorded in people who had previously received immunotherapy or chemotherapy.
Treatment was linked to medically significant side effects in about two-thirds of participants, often involving declines in blood cell counts. There were no cases of neuropathy or drug-related lung disease, nor did any participant discontinue the drug due to treatment-related adverse events.
Further late-stage testing is planned, the abstract notes, and a Phase 3 study of SKB264 in lung cancer was recently posted by a Kelun affiliate on a federal database of clinical trials. Another Phase 3 study in China is set to test the drug in breast cancer, for which a TROP-2 targeting drug from Gilead is currently approved in the U.S.
In a statement, Merck said it plans to “rapidly advance” clinical development of SKB264, and intends to study it in combination with its immunotherapy Keytruda.
“Antibody-drug conjugates are one area we’re exploring in our pipeline, as advances in ADC technologies have greatly improved and we are excited by the potential to more precisely target and deliver potent anticancer agents to the tumor site,” a company spokesperson said in an email to BioPharma Dive.
Partners Daiichi Sankyo and AstraZeneca are also studying an anti-TROP2 ADC in lung cancer, and a study abstract published Thursday revealed updated data from a Phase 1b trial of it in advanced non-small cell lung cancer. AstraZeneca, which paid a significant sum to collaborate with Daiichi Sankyo, is hoping the drug, called datopotamab deruxtecan can be as successful as another ADC, Enhertu, that the companies developed together.
Notably, Daiichi’s study tested datopotamab deruxtecan alongside immunotherapy in some patients who had not received other prior treatment — a particularly competitive first-line setting.
For BioNTech, Thursday’s data release showcased early data on DB-1303, an ADC from DualityBio that targets the well-known breast cancer protein HER2. A total of 85 patients with previously treated HER2-expressing solid tumors had received DB-1303 through mid-January. Of the 52 that had at least one tumor scan post treatment, 23, or 44%, had a partial tumor response, including 50% of participants with HER2-positive breast cancer. Five of those responding patients had metastases in the brain.
There were no dose-limiting toxicities reported, according to the abstract. Side effects most commonly included nausea, vomiting and low platelet counts. The study is continuing to treat patients at the selected dose recommended for further testing.
Other notable datasets featuring ADC drugs have been selected as “late-breaking” abstracts, and will be disclosed during the meeting, scheduled for June 2-6. These include data from Immunogen’s “Mirasol” study of its newly approved ovarian cancer drug Elahere and results from a basket trial testing Daiichi and AstraZeneca’s Enhertu in multiple tumor types.
Experimental therapies aimed at new targets of interest, like Claudin 18.2 and ITGB6, could also draw attention at the meeting.