Merck, Daiichi Sankyo report Phase 2 ADC results in small cell lung cancer, bispecific combo strategy

Recent results from mid-stage clinical trials underscore why Merck and Daiichi Sankyo have advanced an antibody-drug conjugate (ADC) from their $4 billion partnership to Phase 3 studies for a particularly aggressive form of lung cancer.

In the Phase 2 IDeate-Lung01 trial, patients with small cell lung cancer were administered either 8 mg/kg or 12 mg/kg of ifinatamab deruxtecan, known as I-DXd, every three weeks. Among the 42 patients who received the higher dose, 23 showed a response, translating to a response rate of 54.8%. The median overall survival for this group was 11.8 months, with progression-free survival at 5.5 months. These results are promising for a patient group that has already exhausted other treatment options and has extensive-stage disease.

"In this patient population, we typically expect progression-free survival to be very short — closer to two months rather than four," stated Ken Takeshita, Daiichi Sankyo's global head of R&D.

In contrast, the lower dose group had a response rate of 26.1%, with one patient achieving complete response. The median overall survival for this group was 9.4 months, and median progression-free survival was 4.2 months. These findings were presented at the World Conference on Lung Cancer in San Diego.

Daiichi Sankyo and Merck have now advanced the 12 mg/kg dose to a Phase 3 study, dosing the first patient last month.

I-DXd is an ADC that delivers a toxic payload to cancer cells, similar to other ADCs developed by Daiichi Sankyo, such as Enhertu. However, I-DXd targets the protein B7-H3, which is overexpressed in various cancers, including those of the prostate and esophagus.

Scot Ebbinghaus, Merck's VP of clinical research, pointed out that the companies did not measure B7-H3 expression prospectively in the small cell lung cancer trials but are considering it for other cancers. "In small cell lung cancer, because the expression level is so high across the board, we're doing that retrospectively," he explained. "In other tumor types, we're looking at it more prospectively and as a stratification variable."

"We don't have a test for patient selection yet, but we're definitely considering B7-H3 expression as a crucial part of our development program for I-DXd," he added.

On Sunday, GSK also presented data at the conference on its B7-H3 antibody in extensive-stage small cell lung cancer, which it licensed from Hansoh last year. According to the abstract, the overall response rate was 61.3% at 8.0 mg/kg but 50% at 10 mg/kg. The median overall survival was 9.8 months at the lower dose, and it was not reached at the higher dose.

The ADC, known as HS-20093, is currently being tested against chemotherapy in a Phase 3 trial in China for relapsed small cell lung cancer. The companies aim to expand the clinical development program to the US, EU, and other global regions.

In August, Merck partnered with Daiichi on a bispecific T cell engager for small cell lung cancer, acquired from Harpoon Therapeutics. The collaboration plans to test this bispecific antibody, MK-6070, in combination with I-DXd.

Early data, shared in a WCLC abstract, discussed MK-6070's utility in patients with brain metastases, a common complication in small cell lung cancer. Merck has amended a study inherited from Harpoon to include the combination of I-DXd and MK-6070, which "should be recruiting patients any day now," according to Ebbinghaus.

When questioned about future plans for MK-6070 as a monotherapy or in combination, Ebbinghaus mentioned that it was too early to make definitive plans but emphasized that combining treatments is a high priority.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!