US-based biotechnology company Bolt Biotherapeutics has announced positive topline data from a Phase I trial dose-escalation part investigating BDC-1001 in HER2 solid tumours as a monotherapy or in combination with Bristol Myers Squibb’s Opdivo (nivolumab).

BDC-1001 is an immune stimulator antibody conjugate (ISAC) that targets cells expressing HER2.

The topline data indicated that BDC-1001 was well tolerated at all dose levels and schedules, both as a monotherapy and in combination with Opdivo. The analysis also showed that the target drug exposure levels were achieved near or at the recommended Phase II dose (RP2D) by more frequent administration weekly or every other week.

The drug also showed anti-tumour activity such as multiple partial responses, tumour shrinkage and long-term stable disease at or near the RP2D. The company said that the topline data supports the selection of the RP2D and the advancement of Phase II studies that will further investigate BDC-1001.

The Phase I/II trial (NCT04278144) enrolled more than 100 patients with 16 different HER2-expressing solid tumours from Phase I.

Bolt Biotherapeutics chief medical officer Dr Edith Perez said that BDC-1001 not only achieved target exposure levels but also promising signs of clinical activity as a monotherapy and combination treatment.

The study now will move into Phase II, enrolling patients with HER2-positive colorectal, endometrial, and gastroesophageal cancers and investigating BDC-1001 as a monotherapy. Combination treatment with Opdivo is expected to be initiated in each indication after the demonstration of monotherapy anti-tumour activity.

Bolt also announced its clinical supply agreement with Roche to investigate BDC-1001 as a monotherapy and in combination with Perjeta (pertuzumab) in participants with HER2-positive metastatic breast cancer.

The two-cohort Phase II trial will enrol patients who have developed tumours progressing after receiving treatment with Enhertu (trastuzumab deruxtecan), which is co-marketed by Daiichi Sankyo and AstraZeneca. Preclinical studies have shown that Perjeta with a BDC-1001-surrogate demonstrated anti-tumour efficacy in multiple models. This gives a mechanistic rationale to conduct a trial in patients.

With many advancements in the breast cancer space, sponsors and researchers are considering how a patient’s age can factor into it due to the number of women under the age of 60 participating in trials increasing drastically. As many breast cancer trials do not take fertility into account, this puts potential negative effects on participants’ fertility. Clinical Trials Arena spoke with experts on how additional study design parameters can alleviate fertility risks.