The triplet regimen of the CXCR4 inhibitor BL-8040, pembrolizumab, plus chemotherapy demonstrated high response and disease control rates in patients with metastatic pancreatic adenocarcinoma, according to preliminary findings from the COMBAT/KEYNOTE-202 trial that were announced in a press release from BioLineRx Ltd, the developer of BL-8040.
The triplet regimen of the CXCR4 inhibitor BL-8040, pembrolizumab (Keytruda), plus chemotherapy demonstrated high response and disease control rates in patients with metastatic pancreatic adenocarcinoma, according to preliminary findings from the COMBAT/KEYNOTE-202 trial that were announced in a press release from BioLineRx Ltd, the developer of BL-8040.
As of the September 30, 2019, cutoff date, 15 of the 22 patients dosed were evaluable. Four partial responses were observed, and an additional 8 patients had stable disease. This led to a disease control rate in 12 of the 15 patients.
The combination therapy was well tolerated with no unexpected safety signals. Ten patients reported 15 serious adverse events (AEs), and 2 patients discontinued study treatment due to serious AEs.
The study contains 2 cohorts. In the first cohort, patients were treated with single-agent BL-8040 daily for 1 week on days 1 through 5, then received a combination of BL-8040 3 times a week and pembrolizumab once every 3 weeks on 3-week cycles. In the second cohort, patients initially received the same monotherapy treatment in the first week, followed by chemotherapy every 2 weeks, pembrolizumab once every 3 weeks, and BL-8040 twice a week. The chemotherapy regimen included intravenous (IV) liposomal irinotecan (Onivyde) followed by leucovorin, followed by IV fluorouracil (5-FU).
COMBAT/KEYNOTE-202 is a phase IIa, open-label, multicenter trial evaluating the efficacy and safety of the triplet regimen. The trial is designed to assess clinical response, safety, and tolerability in over 30 patients. The study is ongoing and enrolling patients in the United States, Spain, and Israel. The primary end point is objective response rate (ORR) by RECIST 1.1 criteria. Secondary end points include ORR by irRECIST, overall survival (OS), progression-free survival (PFS), and disease control. Median PFS and OS data have not yet matured.
To be included on the trial, patients had to be 18 years or older with histologically confirmed metastatic unresectable pancreatic adenocarcinoma with intraductal papillary mucinous neoplasm, and measurable disease. Cohort 1 had to have documented objective radiographic progression after stopping frontline treatment. Cohort 2 had to have documented objective radiographic progression after stopping frontline gemcitabine-based chemotherapy. In this cohort, patients also had to have primary metastatic disease and could not have received previous therapy for pancreatic cancer. All patients had to have an ECOG status of 0 or 1 and a life expectancy of at least 3 months.
Patients cannot enroll in the trial if they have a pancreatic tumor other than adenocarcinoma, have active infection that requires systemic therapy, a known additional malignancy that requires treatment, or disease suitable for curative intent treatment. They could not be enrolled on another trial at time of the study or have received a systemic steroid therapy or other form of immunosuppressive therapy within 7 days prior to the first study dose. Patients in cohort 2 could not have a bowel obstruction.
“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. Therefore, it is highly important to develop novel combination treatments that will increase the responsiveness and survival of pancreatic cancer patients to immunotherapy,” said Manuel Hidalgo, MD, PhD, principal investigator of the trial and chief of the Division of Hematology and Medical Oncology, Senior Member of the Meyer Cancer Center at Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center, in a press release. “We are encouraged by these preliminary results and look forward to sharing additional data from this important trial next week at [European Society of Medical Oncology Immuno-Oncology (ESMO-IO) Congress].”
CXCR4 is a chemokine receptor that is overexpressed in pancreatic ductal carcinoma, as well as other human cancers. Prior studies suggest it plays a key role in tumor growth, invasion, angiogenesis, metastasis, and resistance to therapy.
Updated data from the COMBAT/KEYNOTE-202 will be presented at the ESMO-IO Congress, taking place in Geneva, Switzerland, December 11 to 14, 2019. Survival data are on track for mid-2020.
BioLineRx Announces Preliminary Phase 2a Data from Triple Combination Arm of COMBAT/KEYNOTE-202 Study in Second Line Patients With Metastatic Pancreatic Cancer. PR Newswire website.https://prn.to/2DPwgAn. Published December 5, 2019. Accessed December 6, 2019.