Pamrevlumab Fails to Improve Survival in 2 Late-Stage Pancreatic Cancer Studies

Microscopic image of pancreatic cancer tumor - Generated with Google Gemini AI

Two studies looking at pamrevlumab (FG-3019), an investigational treatment for pancreatic cancer, failed to meet their primary end points of overall survival (OS).¹

The phase 2/3 Precision Promise study (NCT04229004) sponsored by the Pancreatic Cancer Action Network (PanCAN) investigated pamrevlumab plus gemcitabine and nab-paclitaxel vs gemcitabine and nab-paclitaxel alone in first- and second-line metastatic pancreatic ductal adenocarcinoma (PDAC). The pamrevlumab arm did not show an improvement in OS according to the protocol’s prespecified Bayesian statistical analysis (HR, 1.170; 95% CI, 0.882-1.563; P =.13977).

Additionally, the phase 3 LAPIS study (NCT03941093) comparing gemcitabine and nab-paclitaxel or oxaliplatin, folinic acid, irinotecan, and fluorouracil (FOLFIRINOX) with and without pamrevlumab also failed to show an OS improvement with the addition of pamrevlumab. The median OS was 17.3 months in the pamrevlumab arm vs 17.9 months in the comparator arm (HR, 1.08; 95% CI, 0.83-1.41; stratified log-rank P =.55).

“We are deeply disappointed that the pamrevlumab arm in the Precision Promise trial and the LAPIS trial did not meet the primary end point of overall survival,” said Thane Wettig, chief executive officer of FibroGen, in a press release. “We were hopeful that pamrevlumab could bring meaningful innovation to pancreatic cancer patients 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.”

Pamrevlumab is a potential first-in-class anti-connective tissue growth factor (CTGF) monoclonal antibody. The FDA previously granted pamrevlumab a fast track designation for the treatment of locally advanced pancreatic cancer and an orphan drug designation for the treatment of PDAC.

About the Precision Promise Trial

The phase 2/3 Precision Promise trial enrolled an estimated 825 patients with metastatic PDAC eligible for treatment in first- and second-line settings across 25 locations in the US.² The study’s primary end point was OS, and secondary end points included progression-free survival (PFS), patient performance status, overall response rate (ORR), duration of response, and duration of clinical benefit.

Patients were randomized to receive gemcitabine plus paclitaxel, FOLFIRINOX, or pamrevlumab with nab-paclitaxel and gemcitabine. The study also included 2 additional experimental arms of canakinumab (Ilaris) and spartalizumab plus nab-paclitaxel and gemcitabine and SM-88 plus methoxsalen (Oxsoralen-Ultra), phenytoin (Phenytek), and sirolimus (Rapamune). All experimental arms were closed to patient enrollment.

About the LAPIS Trial

The phase 3 LAPIS study enrolled 284 patients with locally advanced, unresectable pancreatic cancer across 90 locations.³ The study’s primary end point was OS, and secondary end points included event-free survival, PFS, and best ORR. Patients were randomized 1:1 to receive gemcitabine and nab-paclitaxel or FOLFIRINOX with pamrevlumab or placebo.

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 August 1, 2024. https://tinyurl.com/ycxf456f

2. A multi-center trial to evaluate multiple regimens in metastatic pancreatic cancer. ClinicalTrials.gov. Updated March 26, 2024. Accessed August 1, 2024. https://www.clinicaltrials.gov/study/NCT04229004

3. Evaluation of efficacy and safety of neoadjuvant treatment with pamrevlumab in combination with chemotherapy (Either gemcitabine plus nab-paclitaxel or FOLFIRINOX) in participants with locally advanced pancreatic cancer (LAPIS). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03941093