The FDA has granted a Fast Track designation to pamrevlumab for the treatment of patients with locally advanced, unresectable pancreatic cancer, according to FibroGen, the manufacturer of the first-in-class anti-CTGF antibody.
Peony Yu, MD
The FDA has granted a Fast Track designation to pamrevlumab (FG-3019) for the treatment of patients with locally advanced, unresectable pancreatic cancer, according to FibroGen, the manufacturer of the first-in-class anti-CTGF (connective tissue growth factor) antibody.
The Fast Track designation was based on the review of a phase II trial evaluating the safety and efficacy of pamrevlumab in combination with gemcitabine and nab-paclitaxel (Abraxane). The Fast Track program is designed to accelerate the development, review, and approval of drugs that treat serious and life-threatening conditions. As a result of the program, FibroGen will be able to interact with the FDA more often to aid in the expedited development of the agent.
“There are no approved treatment options for patients with locally advanced pancreatic cancer, who face a short life expectancy. We are encouraged by our phase II study results, where the combination of pamrevlumab with chemotherapy changed eligibility for surgical resection in a majority of treated patients who were previously not candidates for surgery,” said Peony Yu, MD, the chief medical officer of FibroGen, in a statement. “This designation is an important milestone for our pamrevlumab program and has the potential to speed our ability to advance pamrevlumab to patients.”
In the trial, patients with locally advanced prostate cancer were randomized 2:1 to gemcitabine/nab-paclitaxel with pamrevlumab or gemcitabine/nab-paclitaxel alone for 6 cycles over a 24-week period. If patients were considered resectable or borderline resectable, had a partial or complete response to treatment, improved CA 19-9 and SUVmaxlevels, they would go on to surgery. Investigators assessed safety and efficacy, including resection rate, overall survival (OS), progression-free survival (PFS), and tumor response.
A total of 33 patients were enrolled on the 2-arm trial. Arm A included 22 patients who received gemcitabine/nab-paclitaxel with pamrevlumab. Nine of the patients in Arm A completed treatment and 3 patients discontinued treatment. Seven patients were eligible for surgical exploration. Three patients underwent R0 resection and 1 patient underwent R1 resection. Resection was not achieved in 3 patients. Arm B included 11 patients who received gemcitabine and nab-paclitaxel alone. Six patients on Arm B completed treatment and 5 patients discontinued treatment. One patient was eligible for surgical exploration and underwent R0 resection.
The primary reasons for treatment discontinuation in Arm A were progressive disease (n = 1), adverse event (AE; n = 1), and physician decision (n = 1). In Arm B, patients discontinued treatment due to progressive disease (n = 2), AE (n = 1), withdrawn consent (n = 1), and combination AE/patient decision (n = 1).
The median PFS in Arm A was 18.4 months and the median PFS in Arm B was 10.1 months. The median OS was not yet met with the combination regimen compared with 18.6 months with gemcitabine/nab-paclitaxel. Investigators noted an early reduction in CA 19-9 levels in Arm A.
Seventeen patients (77.3%) in Arm A experienced treatment-emergent adverse events (TEAEs) and 10 patients (10.9%) in Arm B experienced TEAEs. Ten patients (45.5%) in the investigational arm experienced a TEAE possibly related to pamrevlumab, and 17 patients (77.3%) had a TEAE possibly related to gemcitabine/nab-paclitaxel. A total of 7 patients (31.8%) in Arm A experienced serious TEAEs compared with 4 (36.4%) in Arm B.
“The combination of gemcitabine, nab-paclitaxel, and pamrevlumab is feasible and well tolerated with no incremental safety signals in this study. The addition of pamrevlumab suggests a trend toward increased resectability among locally advanced pancreatic cancer subjects,” lead study author Vincent J. Picozzi, MD, of Virginia Mason Medical Center, and coinvestigators concluded in their study.
Picozzi VJ, Rocha FG, Helton S, et al. Randomized, open-label trial of gemcitabine/nab-paclitaxel (G/NP) ± pamrevlumab (P) as neoadjuvant chemotherapy in locally advanced, unresectable pancreatic cancer (LAPC).J Clin Oncol.2018;36(suppl 4S; abstr 365).