Rafael Pharmaceuticals Announces Initiation of Pivotal Phase 3 Trial (AVENGER 500) of CPI-613 (devimistat) in Combination with Modified FOLFIRINOX as First Line Treatment for Patients with Metastatic Pancreatic Cancer

Interim analysis expected as early as Q2 2020

Newark, NJ, Dec. 11, 2018 (GLOBE NEWSWIRE) -- Rafael Pharmaceuticals, Inc. (Rafael), a leader in the growing field of cancer metabolism-based therapeutics, today announced the initiation of a phase 3 multicenter, open-label, randomized pivotal trial (AVENGER 500) to evaluate the efficacy and safety of its lead compound CPI-613 (devimistat) in combination with modified FOLFIRINOX (mFFX) as first-line therapy in patients with metastatic adenocarcinoma of the pancreas.

AVENGER 500 will compare the efficacy and safety of FOLFIRINOX (FFX, control arm) with CPI-613 in combination with mFFX. Patients 18-75 years old of both sexes with metastatic (stage IV) pancreatic adenocarcinoma, not previously treated for metastatic disease and with ECOG performance status of 0 – 1 are eligible for enrollment in this study. The interim analysis of the study is expected to be completed as early as Q2 2020. More information on the trial is available at www.clinicaltrials.gov (NCT03504423).

An earlier Phase 1 single-center, open-label, dose-escalation study (CCCWFU 57112, NCT01835041) evaluated the safety, tolerability and efficacy of CPI-613 in combination with mFFX as frontline therapy in patients with metastatic pancreatic cancer. A total of 18 patients were treated at the maximum tolerated dose of 500 mg/m2. Overall, the treatment was well tolerated. No deaths due to adverse events were reported and no patients died while on active treatment. Of the 18 patients given the maximum tolerated dose, 3 had a complete radiographic response, 61% achieved an objective response (OR) with a median overall survival (OS) of 19.9 months and median progression free survival (PFS) of 9.9 months. Given these results, further evaluation of CPI-613 in pancreatic cancer was warranted.

Howard Jonas, Chairman of Rafael Pharmaceuticals, commented: “It is our goal not only to prolong life but ultimately to develop cures for pancreatic cancer and other difficult-to-treat cancers. We have great hope both for the success of this trial and for our follow-on compounds in the years to come. We are optimistic that cancer metabolism drugs will create a new paradigm in oncology treatment.”

Sanjeev Luther, President and Chief Executive Officer of Rafael Pharmaceuticals, commented: “Our motto, ‘To Save A Life Is To Save A Universe,’ reflects our commitment to develop potential treatments for patients with significant unmet clinical needs. Pancreatic cancer is one of the most difficult-to-treat cancers. In the last two decades, the median overall survival following standard frontline therapies in metastatic pancreatic cancer has increased to 11.1 months (FOLFIRINOX). Pancreatic cancer is expected to become the second leading cause of cancer related death after 2020. Our focus is on extending and enhancing the lives of patients with pancreatic and other gastrointestinal cancers. Initiation of the AVENGER 500 trial represents a significant milestone in that direction. Given that the clinical development of CPI-613 started at Wake Forest Baptist Health, we wanted this to be the site to enroll the first patient. We are grateful to all the individuals that have been involved with clinical development of CPI-613. Given the importance of this trial we have partnered with a reputable contract research organization, Covance, for study execution.”

Philip A. Philip, MD, PhD, FRCP, the Principal Investigator of this study, commented: “Pancreatic cancer is the deadliest cancer worldwide with very limited treatment options. The current data on CPI-613 in combination with modified FOLFIRINOX in patients battling pancreatic cancer is immensely promising. I am, therefore, delighted to be involved in this important phase 3 trial.”

Timothy Pardee, MD, PhD the Chief Medical Officer of Rafael Pharmaceuticals commented: “I am very excited to see the initiation of this phase 3 trial for metastatic pancreatic cancer patients. There is a clear unmet medical need for this population.”

John Ratliff, Chief Executive Officer of Covance, commented: “We welcome the opportunity to support the Rafael team and broader pancreatic cancer community with the AVENGER 500 trial. We are driven by our mission to improve health and improve lives, and we are excited to be working in this area where there are currently limited options for patients.”

About CPI-613:
CPI-613 is a first-in-class drug, developed based on the Altered Metabolism Directed (AMD) platform. CPI-613 targets altered regulation of metabolic processes specific to cancer cells. It is designed to be highly specific, simultaneously attack multiple targets, minimally toxic and have broad spectrum activity across a wide variety of cancers. CPI-613 is being or has been evaluated in 18 ongoing or completed trials as a single agent, as well as in combination with standard drug therapy for hematological malignancies and solid tumors. To date, over 300 patients have received one or more doses of CPI-613. In a dose escalation study evaluating the safety, tolerability and efficacy of CPI-613 in pancreatic cancer, CPI-613 in combination with modified FOLFIRINOX exhibited an objective response rate of 61%, median overall survival of 19.9 months and median progression free survival of 9.9 months in 18 patients taking the maximum tolerated dose. In elderly patients with AML, CPI-613 in combination with high dose cytarabine and mitoxantrone exhibited 52% CR+CRi and 12.4 months median overall survival. In T-cell lymphoma, CPI-613 in combination with bendamustine exhibited 75% objective response rate. CPI-613 has been granted orphan drug designation by the U.S. FDA for pancreatic cancer, AML, MDS, peripheral T-cell lymphoma and Burkitt’s lymphoma. The EMA has granted orphan drug designation to CPI-613 for pancreatic cancer and AML.

About Pancreatic Cancer:
Pancreatic cancer is an extremely deadly disease , with more than 95% of patients affected dying of their disease1. Although its incidence in the U.S. is relatively low (estimated new cases in 2018 is 55,440)2, pancreatic cancer became the third leading cause of cancer-related deaths in 20163 and is expected to be the second cause of death after 20204 . There are a number of types of pancreatic cancer. The predominant one is adenocarcinoma, which accounts for approximately 95% of exocrine pancreatic cancers.5 Because the disease typically does not present with recognizable/distinctive symptoms in its early stages, when it is diagnosed, it is usually quite advanced and affords limited treatment options. Chemotherapy is the only treatment option for metastatic pancreatic cancer. National Comprehensive Cancer Network (NCCN) treatment guidelines recommend FOLFIRINOX or gemcitabine plus nab-paclitaxel for first-line treatments for patients who are healthy enough to tolerate them and have a support system for a relatively aggressive medical therapy, but efficacy response is limited (FOLFIRINOX6: ORR: 31.6%, OS: 11.1, PFS: 6.4; gemcitabine in combination with nab-paclitaxel7: ORR: 23%, OS: 8.5, PFS: 5.5). However, FOLFIRINOX is regarded as too toxic for use in elderly and poor performance status patients. For patients who wish to pursue cancer-directed therapy but cannot manage such aggressive treatments, gemcitabine alone or alternate choices are recommended. In general, clinical trials are highly recommended for patients with metastatic pancreatic cancer. Another option for patients who cannot tolerate the toxic effects of FOLFIRINOX is to be treated with a modified dosing regimen of FOLFIRINOX, which significantly decreases the adverse side effects (neuropathy, diarrhea, neutropenia) associated with FOLFIRINOX. 5-year survival rate of patients with metastatic (stage IV) pancreatic cancer is only 1%.8 There is a great medical need for more effective first-line systemic therapies that are less toxic and more effective.

About Rafael Pharmaceuticals, Inc.
Rafael Pharmaceuticals, Inc. is a privately held clinical-stage, metabolic oncology therapeutics company committed to the development and commercialization of therapies that exploit the metabolic differences between normal cells and cancer cells. Rafael’s primary objective is to develop innovative, highly selective, well tolerated and highly effective anti-cancer agents by selectively targeting altered metabolism in cancer cells. Rafael’s first-in-class clinical lead compound, CPI-613 is being evaluated in multiple Phase 1, 1/2, 2 and 3 clinical studies. The Company's investors include Rafael Holdings, Inc. (NYSE American: RFL). For more information, visit http://www.rafaelpharma.com/.


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  7. Hoff DV, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. New England Journal of Medicine. 2013;369:1691-703
  8. Cancer.org. (2018). Pancreatic Cancer Survival Rates, by Stage. [online] Available at: https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html [Accessed 7 Dec. 2018].

Tim Pardee MD; Ph.D. was the site principal investigator for early Phase 1/2 clinical trials at Wake Forest Baptist Medical Center.
Bayard L. Powell, M.D., Section Chief, Hematology & Oncology, Associate Director for Clinical Research, Comprehensive Cancer Center, Professor, Hematology & Oncology, Wake Forest Baptist Medical Center serves as a member of Rafael Pharmaceuticals Medical Advisory Board.
Boris Pasche MD; Ph.D. Director, Comprehensive Cancer Center and Chairman, Department of Cancer Biology, Wake Forest Baptist Medical Center, serves as a Board Member to Rafael Holdings, Inc. (NYSE American: RFL) which is an investor in Rafael Pharmaceuticals, Inc.

Safe Harbor Statement
This press release contains forward-looking statements. These statements relate to future events or the company’s future financial performance. In some cases, you can identify forward-looking statements by terminology such as "may", "will", "should", "expect", "plan", "anticipate", "believe", "estimate", "predict", "potential" or "continue", the negative of such terms, or other comparable terminology. These statements are only predictions. Actual events or results may differ materially from those in the forward-looking statements as a result of various important factors. Although we believe that the expectations reflected in the forward-looking statements are reasonable, such statements should not be regarded as a representation by the company, or any other person, that such forward-looking statements will be achieved. The business and operations of the company are subject to substantial risks which increase the uncertainty inherent in forward-looking statements. We undertake no duty to update any of the forward-looking statements, whether as a result of new information, future events or otherwise. In light of the foregoing, readers are cautioned not to place undue reliance on such forward-looking statements.

Sanjeev Luther
President & CEO Rafael Pharmaceuticals, Inc. 

Jacob Jonas
Public Relations, Rafael Pharmaceuticals, Inc.