Five prime new drug combined with opdivo pancreatic cancer phase 2 clinical failure!

Compiling coco The idea that five prime therapeutics combines its experimental CSF-1 receptor inhibitor, cabiralizumab, with the checkpoint inhibitor of BMS, opdivo, to treat pancreatic cancer is bankrupt On February 18, five prime therapeutics announced that the combination of cabiralizumab (Kabila mAb) and opdivo (novolumab) in cooperation with BMS failed to reach its main end point in the treatment of advanced pancreatic cancer stage 2 (nct03336216) The share price of five prime biotechnology fell about 10% after the news In terms of the goal of treating pancreatic cancer, failure is not surprising Pancreatic cancer is one of the diseases with the lowest success rate in biopharmaceutical oncology "Pancreatic cancer is a difficult disease to treat Unfortunately, in this randomized controlled phase 2 clinical trial, neither the combination of cabiramab and opdivo nor the combination of chemotherapy showed more benefits than the standard nursing chemotherapy regimen." Said Dr Helen Collins, executive vice president and chief medical officer of five prime It is reported that about 160 patients with locally advanced or metastatic pancreatic cancer who have progressed after local chemotherapy or first-line chemotherapy in this multi arm, randomized controlled phase 2 study were divided into 4 treatment groups, and received gemcitabine / paclitaxel (Abraxane) or 5-fluorouracil / calcium folinate / irinotecan liposome (onivde) or folic acid / fluorouracil / irinotecan hydrochloride (FOLFIRI) respectively MAb and opdivo; Kabila mAb and opdivo combined with gemcitabine and paclitaxel; Kabila mAb and opdivo combined with oxaliplatin / 5-fluorouracil / folic acid Specific analysis data from BMS led trials were not published, but it noted that no new safety issues were observed with combination therapy in phase 2 trials In October 2015, BMS obtained the development and commercial rights of Kabila mAb from five prime according to the global exclusive license and cooperation agreement, and could choose to jointly promote the drug in the United States After the failure of this study, BMS said that although it had no plans to further sponsor the development of cabilamab in the near future, it would continue to support the ongoing trials of cabilamab and may continue to evaluate the future development opportunities of the experimental drug Cooperative development project between five prime and BMS Source: five prime therapeutics official website In several preclinical models of cancer, it was found that inhibition of colony-stimulating factor-1 receptor (CSF-1R) can reduce the number of immunosuppressive tumor-related macrophages (TAM) in tumor microenvironment, thus promoting the immune response to tumor Cabiralizumab is an in-situ antibody that inhibits the CSF-1R receptor It has been shown that it can block the activation and survival of monocytes and macrophages in preclinical models and clinical studies Mechanism of action of cabiralizumab Source: five prime therapeutics official website The failure has brought another blow to five prime, a biotech company that has struggled in the past 18 months In the fall of 2019, CEO Aron Knickerbocker quit the company Before leaving, Knickerbocker slashed its staff and early research and development programs by 20% to focus on clinical cancer research and development programs Bill Ringo, chairman of the board of directors, took over the position of president, and cut another 70 people after taking office a month later The layoff also forced the company to set up a "small research team" focused on advancing clinical candidate drugs with the help of service providers and contractors During Knickerbocker's tenure, he opened a $1.74 billion partnership with BMS to combine his I-O candidate drug, Kabila mAb, with opdivo Current Five Prime is committed to the development of immunomodulators and precision therapies for solid tumor cancer, including a phase 3 clinical trial of first in class bemarituzumab (fpa144, bemaritozumab) in the treatment of advanced gastric cancer or gastroesophageal junction cancer, which is a fgf2b antibody under development with enhanced antibody dependent cell-mediated cytotoxicity Body selective antibody Five prime is developing drug pipeline