Rutgers trial aims to demonstrate reduction in immune-related adverse events, while adding to anti-cancer immune effects for patients

Nov. 15, 2018:

BeyondSpring Inc. recently announced the opening of an investigator-initiated Phase 1 clinical trial with a triple combination therapy, consisting of BeyondSpring’s lead asset, plinabulin, and Bristol-Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab) for the treatment of small-cell lung cancer (SCLC). The trial (BTCRC-LUN17-127), conducted through the Big Ten Cancer Research Consortium (Big Ten CRC), is currently enrolling subjects at Rutgers Cancer Institute of New Jersey. Jyoti Malhotra, MD, MPH, medical oncologist at Rutgers Cancer Institute, is the trial’s sponsor-investigator. The trial is expected to enroll approximately 15 patients in the Phase 1 portion of this Phase 1/2 combined study, and an additional 40 patients in the Phase 2 portion.

“Our collective mission is to bring the best possible therapy to SCLC patients around the world as quickly and efficiently as we can,” said Dr. Malhotra. “There is a need to explore novel immunotherapy combinations with the goal of improving clinical outcomes as well as reducing side effects.”

Approximately 10 to 15 percent of lung cancers are SCLC. Although it is less common than non-small cell lung cancer (NSCLC), SCLC is more aggressive, as these cancer cells tend to grow rapidly and metastasize more easily. Related to this, SCLC symptoms usually do not surface in patients until the cancer has progressed to a more advanced stage, setting a higher bar for therapeutic benefit.

Plinabulin is a novel small molecule with immune-enhancing effects and anti-cancer activity that induces dendritic cell maturation and T-cell activation. Plinabulin is in advanced Phase 3 testing to both increase the potency of standard-of-care chemotherapy (i.e., docetaxel), while at the same time alleviating chemotherapy-induced side effects. The aim of the present triple combination study is to accomplish similar goals with the standard-of-care immuno-oncology (I/O) therapies by reducing treatment-related side effects and increasing the therapeutic benefit to patients.

“Given that plinabulin is also in Phase 3 clinical trials for both NSCLC treatment and the prevention of chemotherapy-induced neutropenia, this drug candidate is an I/O molecule with multiple possible indications,” concluded Dr. Ramon Mohanlal, executive vice president and chief medical officer at BeyondSpring. “Plinabulin is not just a compound — it is a pipeline drug. Up to this point, the research around plinabulin has advanced positively and significantly.”

About Plinabulin: Plinabulin, a marine-derived small-molecule, is BeyondSpring’s lead asset and is currently in late-stage clinical development for the prevention of CIN and as an anticancer therapy in NSCLC. Studies of Plinabulin’s mechanism of action indicate that plinabulin activates GEF-H1, a guanine nucleotide exchange factor. GEF-H1 activates downstream transduction pathways leading to the activation of the protein c-Jun. Activated c-Jun enters the nucleus of dendritic cells to up-regulate immune-related genes, which contributes to the up-regulation of a series of genes leading to dendritic cell maturation, T-cell activation, and other effects that prevent neutropenia by reducing the neutrophil breakdown.

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to almost 9,500 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit