Phase 2 Trial Shows Dalantercept Has Limited Effectiveness in Ovarian Cancer Patients

Phase 2 Trial Shows Dalantercept Has Limited Effectiveness in Ovarian Cancer Patients

A Phase 2 clinical trial determined that treatment with dalantercept, an inhibitor of blood vessel maturation, is safe but has limited effectiveness in ovarian cancer patients, none of whom responded to the investigational therapy.

The clinical development of the investigational therapy has been discontinued.

Trial findings were published in the study, “Phase II evaluation of dalantercept in the treatment of persistent or recurrent epithelial ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study,” in the journal Gynecologic Oncology.

Angiogenesis, which refers to the formation of new blood vessels, is essential during normal growth and development. It also plays a critical role in the growth and spread of cancer cells, since it ensures a supply of blood to the newly spread cancer cells.

As a result, targeting angiogenesis is one strategy that can be used to combat cancer.

There are two main steps involved in angiogenesis: activation — where blood vessel-forming cells divide — and maturation. The current rationale is that blocking the maturation phase may be a broader approach for cancer treatment.

The activin receptor-like kinase 1 (ALK1) protein is involved in the maturation phase and is therefore a potential therapy target. Dalantercept, by Acceleron Pharma, is a synthetic protein that blocks ALK1 activity and had proven promising in a Phase 1 trial involving 37 patients with advanced solid tumors.

Based on these results, researchers conducted an open-label Phase 2 trial to determine the anti-tumor activity of dalantercept in ovarian cancer patients.

The study (NCT01720173) included 30 women with recurrent or persistent ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma.

Participants received under-the-skin injections of dalantercept once every 21 days until disease progression or unacceptable toxicity. Treatment effectiveness was assessed by imaging and serum CA-125 levels — a biomarker of ovarian cancer — at the beginning and throughout the study.

Adverse events were mostly mild or moderate, and included anemia, fatigue, fluid in the lungs, and swelling. There were no severe or life-threatening adverse events.

During the study, all patients stopped the treatment — 24 due to disease progression, five for toxicity, and one for other reasons. None of the patients achieved a partial or complete response to treatment, but 11 had their disease stabilized.

Additionally, 20% of patients remained without disease progression or the need for additional therapies for more than six months. At this point, the treatment was considered to have failed to show sufficient clinical activity for the study to proceed, and the trial was closed.

“Dalantercept demonstrated insufficient efficacy to warrant further investigation as a single agent for patients with recurrent or persistent ovarian cancer,” the investigators said, concluding that “though safe, dalantercept as administered had limited efficacy in this patient population overall.”

A similar lack of efficacy was also seen a Phase 2 trial (NCT01727336) for renal cell carcinoma — a kind of kidney cancer — which led Acceleron to discontinue dalantercept’s development in 2017.