GENEVA, SWITZERLAND-Updated data from the triple combination arm of the ongoing phase IIa COMBAT/KEYNOTE-202 study was presented at the 2019 ESMO Immuno-Oncology Congress. A total of 36 out of 40 patients have been enrolled in the study. As of December 5, 2019 (the cutoff date for the presentation data), 30 patients were evaluable for safety and 22 were evaluable for efficacy. All patients enrolled were originally diagnosed with stage IV metastatic pancreatic ductal adenocarcinoma (PDAC) and had progressed following first-line treatment with gemcitabine-based chemotherapy.
Best response for the evaluable population of 22 patients showed seven partial response (PR) and 10 stable disease (SD) patients, resulting in an overall response rate (ORR) of 32 percent and a disease control rate (DCR) of 77 percent; this compares favorably to the current chemotherapy standard-of-care treatment in second-line patients with ORR of 17 percent and DCR of 52 percent.
The combination showed continuity of effect-five patients with stable disease became partial responders as treatment continued.
Out of the seven partial responders, five are still on treatment, with a current maximum treatment time of 330+ days; and four responders showed a reduction in tumor burden of >50 percent.
Median duration of clinical benefit until progression for the 17 patients with disease control (seven PR and 10 SD patients) is 7.8 months.
The study is ongoing; progression-free and overall survival data remain on track for mid-2020.
The combination was generally well-tolerated, with a safety profile consistent with the individual safety profile of each component alone; adverse event (AE) and severe adverse event (SAE) profiles are as expected with chemotherapy-based treatment regimens.
"Metastatic pancreatic cancer has a very poor response to chemotherapy, and immunotherapy treatments have failed to show any effect as single agents," said Manuel Hidalgo, MD, PhD, Chief of the Division of Hematology and Medical Oncology and a senior member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center, and principal investigator of this study.
"These promising initial results presented today show an overall response rate almost double the current chemotherapy standard-of-care treatment in second-line patients. The results are even stronger when taking into account the extended durability of clinical benefit seen to date in this study (median of 7.8 months), compared to approximately three months of response duration with other treatments for second-line pancreatic cancer. I look forward to the survival data expected in mid-2020."
Study Details
The triple combination arm focuses on second-line pancreatic cancer patients and is expected to include approximately 40 patients originally diagnosed with unresectable metastatic pancreatic adenocarcinoma who have progressed following first-line gemcitabine-based therapy. Patients receive BL-8040 monotherapy priming treatment for five days, followed by combination cycles of chemotherapy (irinotecan liposome injection/5-fluorouracil/leucovorin), pembrolizumab, and BL-8040 until progression. The primary endpoint of the study is the objective response rate (ORR). Secondary endpoints include overall survival, progression-free survival, and disease control rate.
The phase IIa COMBAT/KEYNOTE-202 study was originally designed as an open-label, multicenter, single-arm trial to evaluate the safety and efficacy of the combination of BL-8040 and pembrolizumab, an anti-PD-1 therapy, in over 30 subjects with metastatic pancreatic adenocarcinoma. The study was primarily designed to evaluate the clinical response, safety and tolerability of the combination of these therapies, and was carried out in the U.S., Israel, and additional territories.