ASCO Focuses on Advancing Antibody-Drug Conjugate Pipeline

The last few years have brought a revival in the development of a complex but powerful type of cancer treatment. Known as antibody-drug conjugates, or ADCs, these therapies have become a must-have for pharmaceutical companies serious about oncology research — a change 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 dozens of presentations on studies testing ADCs in various types of cancer.

Abstracts summarizing the results of many of these trials were published online Thursday, including for the first closely watched 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 under separate agreements with, respectively, Chinese companies Kelun Biotech and Duality Biologics. The summaries leaked on Thursday give investors and analysts who watch the companies better insight into why the drugmakers reached a deal.

Merck’s new drug, dubbed SKB264, targets a protein known as TROP2 that is 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 linked via a binding molecule to a toxic derivative of the chemotherapy belotecan.

Study data included in the abstract shows that SKB264 reduced tumors in 44% of 39 participants with advanced lung cancer who were evaluable for a response. Responses were recorded in people who had previously received immunotherapy or chemotherapy.

The treatment was linked to medically significant side effects in about two-thirds of the participants, often involving a drop in blood cell counts. There were no cases of drug-related neuropathy or lung disease, and no participants discontinued 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 published by a Kelun subsidiary on a federal clinical trials database. Another Phase 3 study in China is set to test the drug in breast cancer, for which a drug targeting Gilead’s TROP-2 is currently approved in the United States.

In a statement, Merck said it plans to “quickly advance” the clinical development of SKB264, and intends to study it in combination with its Keytruda immunotherapy.

“Antibody-drug conjugates are an area we are exploring in our pipeline as advances in ADC technologies have improved dramatically and we are excited about the potential to more precisely target and deliver potent anti-cancer agents to the tumor site” , said a spokesperson for the company. in an email to BioPharma Dive.

Partners Daiichi Sankyo and AstraZeneca are also studying an anti-TROP2 ADC in lung cancer, and a study summary released Thursday revealed updated data from a phase 1b trial of it in lung cancer. non-small cell advanced. AstraZeneca, which paid a hefty sum to collaborate with Daiichi Sankyo, hopes the drug, called datopotamab deruxtecan, can be as successful as another ADC, Enhertu, that the companies have developed together.

Notably, Daiichi’s study tested datopotamab deruxtecan alongside immunotherapy in some patients who had not received any other prior treatment – a particularly competitive front-line setting.

For BioNTech, Thursday’s data release presented the first 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 who had at least one tumor scan after treatment, 23, or 44%, had a partial tumor response, including 50% of participants with HER2-positive breast cancer. Five of these responder patients had brain metastases.

According to the abstract, no dose limiting toxicities were reported. Side effects most commonly included nausea, vomiting, and low platelet count. The study is continuing to treat patients at the selected dose recommended for further testing.

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