Adding BL-8040 to Keytruda and Chemo Shows Good Disease Control in Pancreatic Cancer, Phase 2 Trial Shows

Treatment with investigational BL-8040, in combination with Keytruda (pembrolizumab) and chemotherapy, leads to promising response and disease control rates in people with metastatic pancreatic cancer who progressed after first-line therapy, preliminary data from a Phase 2a clinical trial show.

The findings were revealed in an oral presentation, “A Multi-Center Phase 2a Trial to Assess the Safety and Efficacy of BL-8040 (a CXCR4 inhibitor) in Combination with Pembrolizumab and Chemotherapy in Patients with Metastatic Pancreatic Adenocarcinoma (PDAC),” during the recent European Society of Medical Oncology (ESMO) Immuno-Oncology Congress, held Dec. 11–4 in Geneva, Switzerland.

“We are very excited by the preliminary data from this triple combination arm of our Phase 2a pancreatic study under our collaboration with Merck,” Philip Serlin, CEO of BioLineRx, said in a press release.

“Despite metastatic [pancreatic adenocarcinoma] being one of the toughest diseases to treat, with so many prior clinical failures, we believe this combination of BL-8040, Keytruda, and chemotherapy may provide real hope to pancreatic cancer patients,” he said.

BL–8040, developed by BioLineRx, is an immunotherapy that inhibits CXCR4, a receptor involved in tumor growth, metastasis, and resistance to treatment in various types of cancer, including pancreatic. High levels of CXCR4 usually are associated with a poor prognosis.

Clinical and preclinical studies have shown that, besides directly killing tumor cells, BL-8040 changes the tumor microenvironment in multiple ways, increasing the number of immune cells that have the ability to fight cancer, while reducing the infiltration of immunosuppressive cells. This makes the tumor more sensitive to other treatments, such as immunotherapies and chemotherapeutic agents.

Keytruda, developed by Merck (known as MSD outside the U.S. and Canada), is an immune checkpoint inhibitors designed to boost the anti-tumor response of immune cells. It blocks the interaction between the PD-1 receptor with its ligands, an interaction used by cancer cells to evade immune system attack.

While proven effective in multiple cancer types, Keytruda has been mostly ineffective in pancreatic cancer, likely due to the “cold” — devoid of immune cells — nature of these tumors.

The ongoing COMBAT/KEYNOTE-202 Phase 2a trial (NCT02826486) was designed to test if BL-8040 could increase the sensitivity of pancreatic cancers to Keytruda, increasing patient responses and survival outcomes, compared to what had been seen in other Keytruda trials.

The trial is recruiting people with inoperable, metastatic pancreatic cancer who received gemcitabine-based chemotherapy as their first-line therapy. It has two arms, one testing the combination alone and a second testing the combination along with chemotherapy (Onivyde plus leucovorin and 5FU).

Findings from the first group showed that the Keytryda, BL-8040 combination was safe and effective, with patients living a median of 7.5 months, which was deemed “promising.” Researchers now presented data from the second group of patients, who received that same combination along with standard chemotherapy.

At the time of data cut-off (September 2019), 22 of 40 planned participants had been dosed. Among the 15 patients evaluable for efficacy analysis, four had a partial response to the combination and an additional eight had stable disease. This represented a response rate of 27% and a clinical benefit rate of 80%.

The study has not yet gathered enough data to calculate the median progression-free survival (the time patients are alive and without disease progression) and overall survival. Those results are expected by mid-2020.

The combination was overall well-tolerated, with a safety profile similar to that of the individual treatments. Ten patients reported a total of 15 serious adverse events (side effects), and two discontinued the trial because of that.

“Metastatic pancreatic cancer has the worst prognosis of all solid tumors, with five-year survival rates of 3%, and a very poor response to the currently available immunotherapy treatments that are transforming care in other cancer indications,” said Manuel Hidalgo, MD, PhD, principal investigator of the COMBAT trial.

“It is highly important to develop novel combination treatments that will increase the responsiveness and survival of pancreatic cancer patients to immunotherapy,” Hidalgo added.