SAN FRANCISCO - On the fourth day of the 38th annual JP Morgan Healthcare Conference, Five Prime Therapeutics provided an update on the development of bemarituzumab and FPA150, and Gritstone Oncology discussed plans for its personalized immunotherapies. Below are brief reports on the presentations covered by our team at the conference and in our offices in New York.
Helen Collins, CMO of Five Prime Therapeutics, provided development updates for its five clinical programs, three of which are partnered with Bristol-Myers Squibb. As a result of company restructuring efforts, Five Prime has shifted its focus away from early discovery programs, which should reduce its cash burn for operating activities this year by about $40 million compared to last year. Instead, Collins said the firm will focus on developing its clinical-stage programs, especially bemarituzumab for FGFR2b overexpressing gastric and gastroesophageal junction cancer, and FPA150 for B7-H4 overexpressing breast, ovarian and endometrial cancer.
Bemaritizumab blocks FGFR2b activation, which enhances cancer cell killing. Approximately 30 percent of front-line gastric cancer is FGFR2b positive. The company is hoping that the antibody's specificity will make it less toxic than oral FGFR tyrosine kinase inhibitors. There is an ongoing Phase III trial testing the bemaritizumab with chemotherapy which currently comprises 150 gastric cancer patients. In the Phase I trial, researchers saw an 18 percent overall response rate in patients with late gastric cancer.
FPA150 targets B7-H4 and is a novel checkpoint inhibitor. B7-H4 is overexpressed in multiple solid tumors, but not in normal cells, which limits off-target toxicity, according to the company. It is currently being studied in a Phase I trial in combination with Keytruda in B7-H4-positive ovarian cancer and the drug has been well-tolerated to date. Efficacy from this trial should be read out sometime mid-year.
Gritstone CEO Andrew Allen presented patient data from the Phase I GRANITE-001 and SLATE-001 studies and laid out development plans for the two artificial intelligence-based immunotherapies. Gritstone also has plans to leverage its EDGE platform to develop bispecific antibodies.
GRANITE is a personalized immunotherapy where an individual patient's tumor-specific targets or neoantigens are integrated into vectors and injected into patients along with immunotherapy and the anti-PD-1 drug nivolumab (BMS' Opdivo). Last December, Gritstone reported that GRANITE was well tolerated in patients.
In the Phase I cohort of six total patients, no dose-limiting toxicity has been observed at the data cut-off on Jan 6. One patient had non-small cell lung cancer. Two patients had microsatellite stable colorectal cancer. Three patients had gastroesophageal adenocarcinoma. A 76-year-old male with metastatic gastroesophageal junctional adenocarcinoma had stable disease for 6 months in response to GRANITE and progressive disease at week 24. Another 60-year-old male with metastatic gastroesophageal junction adenocarcinoma had disease control for 8 months so far. A 72-year-old female with stage IIIB NSCLC and progression following prior treatments was clinically stable but had progressive disease at week 8 and was treated beyond progression.
The Phase II trial for GRANITE will be divided into a single-arm study of patients with advanced tumors and a randomized adjuvant study in high-risk localized tumors. In the single-arm study, Gritstone has a target overall response rate of 15 percent for microsatellite stable-CRC patients and 30 percent for gastroesophageal adenocarcinoma patients. In the adjuvant study, the tumor types being observed are NSCLC and GEA and the primary endpoint is recurrence free survival.
SLATE has a common set of neoantigens based on 20 cancer-driving mutations shared across patients. These mutations include KRAS G12D, G12A, G12C, G12V and others. All patients in the Phase I/II study will also receive nivolumab. No dose-limiting toxicity was observed in the four patients tested, which included three with NSCLC and one had microsatellite stable-CRC. An 84-year-old female with stage IV KRAS G12C mutated NSCLC had a drop in circulating neoantigen DNA, which correlated with a 20 percent tumor reduction at week 8, and was confirmed by CT scan.
The Phase II trial for SLATE will also be divided into a single-arm study in patients with advanced tumors and a randomized adjuvant study in high-risk localized tumors. In the single-arm study, Gritstone has a target overall response rate of at least 15 percent for MSS-CRC patients, at least 20 percent for NSCLC, and 20 percent for metastatic pancreatic ductal adenocarcinoma patients. In the adjuvant study, the tumor types being observed are NSCLC, pancreatic ductal adenocarcinoma and microsatellite stable-CRC, and the primary objective is recurrence-free survival.
Gritstone expects to start Phase II trials for both SLATE and GRANITE in the second half of 2020.