The pioneering discovery in the middle of the 20th century that metabolic activity in tumor tissues is different from that of normal tissues. Based on this understanding deregulation of cellular metabolism emerged as a key hallmark of cancer. Scientists found that reprogramming of core cellular metabolic pathways by cancer cells provides energy, anaplerotic precursors and reducing equivalents required to support tumor growth. This insight generated significant interest in developing novel cancer therapies designed to alter the metabolic pathways as a means of limiting the supply of crucial nutrients  to cancer cells.[1]

And while this approach was considered by many scientists to be highly promising, progress in cancer metabolism-based therapeutics has been slow. One of the reasons is the complex nature of these pathways.  However, the improved understanding of cancer metabolism has led to a renaissance of interest in this area.

During the upcoming annual meeting of the American Society of Clinical Oncology (ASCO)  taking place June 3 – June 7, 2022 in Chicago, Cornerstone Pharmaceuticals (previously known as Rafael Pharmaceuticals) and its partners are expected to present three abstracts focusing on rare cancers.

The three abstracts highlight the ongoing development of CPI-613® (devimistat) in clear cell sarcoma and biliary tract cancer, and pancreatic cancer.

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“We are incredibly proud to have promising research findings to share in the three rare cancer areas that we’re focused on at ASCO’s Annual Meeting,” noted Sanjeev Luther, President and Chief Executive Officer of Cornerstone Pharmaceuticals.

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“Our research provides hope for the future as we continue to put patients with rare cancer diagnoses at the forefront and move the needle towards progress for potentially life-saving therapy.” he added.

“As biliary tract cancer cases continue to rise globally, I am pleased to partner with Cornerstone Pharmaceuticals and study the use of devimistat as a potential therapy option for the disease,” Sahai said.

“I look forward to discussing my findings at ASCO with fellow industry professionals as we envision a future that could offer relief to patients who suffer from this aggressive cancer.”

Pancreatic cancer
“It’s an honor to discuss our research in pancreatic cancer with some of the brightest minds in clinical oncology at ASCO,” Philip noted.

“Although pancreatic cancer remains a challenge for both patients and clinicians, devimistat’s promise as a potential treatment option gives us great hope for the future of care.”

“Currently, patients who live with relapsed or refractory clear cell sarcoma (CCS) have limited treatment options,” Agulnik said.

“In partnership with Cornerstone Pharmaceuticals, I am energized by the opportunity to share my research at ASCO on the promising Phase I and Phase II data using devimistat,” he concluded.

Key Presentations
Abstract/Poster*Date/TimePresenting Author
Saturday, June 4, 2022
Time: 8:00 a.m. CDT
Location: Hall A | In-Person & On Demand
Vaibhav Sahai, MBBS, MS,

Associate Professor, University of Michigan Health

Phase 1b results of a multicenter, randomized phase 1b/2 study of gemcitabine and cisplatin +/- CPI-613 as first-line therapy for patients with advanced biliary tract cancer (BilT-04)Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
J Clin Oncol 40, 2022 (suppl 16; abstr 4094)
DOI 10.1200/JCO.2022.40.16_suppl.4094
Saturday, June 4, 2022;

Poster Presentation – 8 a.m. CDT, Poster Discussion Session – 1:15 p.m. CDT

Location: Poster Presentation – Hall A, Poster Discussion Session – McCormick Place: Hall D2 | In-Person & Live Stream

Philip Agop Philip MD, PhD, FRCP, Professor, GI & Neuroendocrine Oncology,

Henry Ford Cancer Institute, Wayne State University School of Medicine

Phase 3, multicenter, randomized study of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) as first-line therapy for patients with metastatic adenocarcinoma of the pancreas (AVENGER500)Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
J Clin Oncol 40, 2022 (suppl 16; abstr 4023) DOI
10.1200/JCO.2022.40.16_suppl.4023
Sunday, June 5, 2022
Time: 8:00 a.m. CDTLocation: Hall A | In-Person & On Demand
Mark Agulnik MD

Northwestern University, Feinberg School of Medicine, Chicago, IL

Phase 1/2 study of devimistat in combination with hydroxychloroquine (HCQ) in patients with relapsed or refractory (R/R) clear cell sarcoma (CCS)Sarcoma
J Clin Oncol 40, 2022 (suppl 16; abstr TPS11595)
DOI 10.1200/JCO.2022.40.16_suppl.TPS11595
Note: * All abstracts are available on the ASCO 2022 conference website #ASCO22

 

Clinical trials
To Evaluate Maximally Tolerated Dose (MTD), Safety and Efficacy of CPI-613® (Devimistat) Plus Hydroxychloroquine in Patients With Relapsed or Refractory Clear Cell Sarcoma of Soft Tissue – NCT04593758
Study Evaluating Efficacy and Safety of FFX Versus Combination of CPI-613 With mFFX in Patients With Metastatic Adenocarcinoma of the Pancreas – NCT03504423
Gemcitabine and Cisplatin With or Without CPI-613 as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer (BilT-04) – NCT04203160

Reference
[1] La Vecchia S, Sebastián C. Metabolic pathways regulating colorectal cancer initiation and progression. Semin Cell Dev Biol. 2020 Feb;98:63-70. doi: 10.1016/j.semcdb.2019.05.018. Epub 2019 May 28. PMID: 31129171.

Featured image: ASCO annual meeting 2019. Photo courtesy: © 2019 – 2022 Sunvalley Communication/Evan Wendt. Used with permission.

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