Pamrevlumab Fails to Provide OS Benefit in Pancreatic Cancer

Two late-stage trials investigating the efficacy and safety of the first-in-class, anti-CTGF monoclonal antibody pamrevlumab in patients with pancreatic cancer failed to meet their primary end points of overall survival (OS).¹

In the phase 2/3 Precision Promise trial (NCT04229004), which compared pamrevlumab plus gemcitabine and nab-paclitaxel (Abraxane) vs gemcitabine plus nab-paclitaxel alone in the first- and second-line settings in patients with metastatic pancreatic ductal adenocarcinoma, the pamrevlumab arm did not achieve a statistically significant OS benefit per the protocol prespecified Bayesian statistical analysis (median Bayesian model common HR, 1.170; mean HR, 1.184 [standard deviation, 0.175]; 95% CI, 0.882-1.563; posterior probability, 0.13977).

Furthermore, the phase 3 LAPIS trial (NCT03941093), which compared neoadjuvant treatment with pamrevlumab plus FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) or gemcitabine and nab-paclitaxel with placebo plus FOLFIRINOX or gemcitabine and nab-paclitaxel in patients with locally advanced, unresectable pancreatic cancer, failed to meet its primary end point of OS (stratified log-rank P = .55). The median OS in the pamrevlumab arm was 17.3 months vs 17.9 months in the control arm (HR, 1.08; 95% CI, 0.83-1.41).

Based on the findings from these trials, FibroGen plans to implement an immediate cost-reduction plan in the United States (US). FibroGen will terminate its pamrevlumab development program and plans to end its remaining obligations associated with the agent.

“We are deeply disappointed that the pamrevlumab arms in the Precision Promise trial and the LAPIS trial did not meet the primary endpoint of OS,” Thane Wettig, CEO of FibroGen, stated in a news release. “We were hopeful that pamrevlumab could bring meaningful innovation to [patients with] pancreatic cancer in desperate need of new therapies. FibroGen would like to thank the patients, their families, and the clinical trial investigators and teams for their dedication to participating in these studies. I would also like to express my deepest gratitude to our FibroGen colleagues who have dedicated so much of their time and energy for the prospect of bringing much-needed therapies to some of the most challenging and deadly diseases affecting humanity.”

The Precision Promise trial enrolled patients at 24 sites across the US. In Precision Promise, since both the first- and second-line treatment groups proceeded into stage 2 of the trial, the primary OS analysis assumed a common HR to estimate a single treatment effect for the pamrevlumab-based combination vs gemcitabine plus nab-paclitaxel alone in both lines of treatment. The prespecified primary efficacy analysis was conducted in a modified intention-to-treat (mITT) population that consisted of 102 first-line and 111 second-line patients who initiated treatment with pamrevlumab. In the control arm, the mITT population consisted of 34 first-line and 36 second-line patients. The final analysis of this trial was based on data that was collected up to 12 months after the last patient began treatment.

The global, double-blind LAPIS trial enrolled 284 patients who received a maximum of 6 treatment cycles. Patients who completed the trial therapy were evaluated for surgical exploration for possible R0 or R1 resection. Patients who were deemed ineligible for surgical exploration continued to receive standard-of-care therapy per their institution’s guidelines.

Preliminary safety analyses across both trials showed that pamrevlumab plus FOLFIRINOX or gemcitabine and nab-paclitaxel was generally well tolerated and had an acceptable safety profile. Investigators observed no clinically meaningful differences in treatment-emergent adverse effects between the treatment arms.

Previously, in 2017, the FDA granted orphan drug designation to pamrevlumab for the treatment of patients with pancreatic cancer.² The agent also received fast track designation in 2018­­­ for the treatment of patients with locally advanced pancreatic cancer.³

References

1. FibroGen announces topline results from two late-stage pamrevlumab pancreatic cancer studies and provides corporate update. News release. FibroGen, Inc. July 30, 2024. Accessed July 31, 2024. https://investor.fibrogen.com/news-releases/news-release-details/fibrogen-announces-topline-results-two-late-stage-pamrevlumab
2. FibroGen granted orphan drug designation for pamrevlumab in the treatment of pancreatic cancer. News release. FibroGen, Inc. June 21, 2017. Accessed July 31, 2024. https://investor.fibrogen.com/news-releases/news-release-details/fibrogen-granted-orphan-drug-designation-pamrevlumab-treatment
3. FibroGen granted fast track designation by U.S. FDA for pamrevlumab treatment of patients with locally advanced unresectable pancreatic cancer. News release. FibroGen, Inc. March 1, 2018. Accessed July 31, 2024. https://investor.fibrogen.com/news-releases/news-release-details/fibrogen-granted-fast-track-designation-us-fda-pamrevlumab