—The study is conducted by the Big Ten Cancer Research Consortium in up to 26 patients across 7 states in the U.S.
—In the Phase 1 study, plinabulin combination was able to induce tumor responses in patients who had progressed on platinum and checkpoint inhibitors, with 43% ORR (3 partial responses with tumor reduction >50%). Duration of treatment was as long as 18 months in 1 patient.
NEW YORK, October 21, 2021 — BeyondSpring (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, announced the first patient has been treated in an investigator-initiated, open-label Phase 2 study with lead asset plinabulin in combination with nivolumab + ipilimumab in patients with 3rd line recurrent small-cell lung cancer (SCLC) who failed checkpoint inhibitors and platinum-based chemotherapy. Plinabulin is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. This Phase 2 study, to be conducted through the Big Ten Cancer Research Consortium in 7 U.S. clinical centers, comes after the successful completion of the Phase 1 dose escalation study portion of this Phase 1/2 study.
“For patients with extensive stage SCLC who failed chemo and checkpoint inhibitors, effective treatment options are limited. By exploring this novel immunotherapy combination and expanding on the encouraging Phase 1 data, there is an opportunity to address this unmet medical need,” commented Jyoti Malhotra, M.D., M.P.H., Principal Investigator, medical oncologist at Rutgers Cancer Institute of New Jersey. “In the Phase 1 study, the addition of plinabulin to nivolumab + ipilimumab was able to induce tumor responses in patients who failed chemotherapy and checkpoint inhibitors with ORR at 43%, double the ORR of nivolumab + ipilimumab in Checkmate 032. An added bonus is the marked reduction in Grade 3/4 IR-AEs from historical 37% to 12.5%; IR-SAE typically leads to permanent discontinuation of PD-1 and CTLA-4 combination. The ability to both enhance the anti-cancer effects and reduce the Grade 3/4 IR-AEs of PD-1 and CTLA-4 inhibitors makes plinabulin an ideal addition to these checkpoint inhibitors for establishing the concept of a ‘chemo-free’ therapeutic strategy for cancer patients.”
In this Phase 2 study, up to 26 patients with histological or cytological confirmed extensive-stage SCLC who progressed after at least one platinum-based chemotherapy regimen and checkpoint inhibitors will receive the triple combination of plinabulin + nivolumab + ipilimumab. Patients in the Phase 2 study will continue treatment until disease progression, development of unacceptable toxicity, or one of the protocol-defined reasons for treatment discontinuation occurs.
Dr. Ramon Mohanlal, BeyondSpring’s Executive VP of R&D and Chief Medical Officer added, “Confirmation of the positive Phase 1 data in Phase 2 will open the doors for adding plinabulin to PD-1 and CTLA-4 inhibitors as a ‘chemo-free’ triple combination therapeutic strategy in the cancer types wherein plinabulin has single agent activity, which include bladder cancer, TNBC, CNS cancers, gastric cancers and sarcoma. We firmly believe that plinabulin’s differentiated immune MOA, as a SIMBA, provides the basis for its potential broad applicability as an anti-cancer agent in multiple cancer indications. The recent success of Dublin-3 showing plinabulin’s durable anti-cancer benefit in long term survivals in NSCLC patients is our first step towards this goal. We’re also very thankful to be working with experts at the Big Ten Research Consortium who realized the potential for plinabulin and chose it to be the subject of this combination therapy clinical trial.”
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected, NDA-stage asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation from both U.S. and China FDA for the CIN prevention indication. As a “pipeline in a drug,” plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients.
SCLC Phase 1 IIT Study (Big Ten Consortium)
In the Phase 1 dose escalation study evaluating 20 mg/m2 and 30 mg/m2 doses of plinabulin combined with nivolumab and ipilimumab in 16 patients, the 30 mg/m2 dose was selected for the Phase 2 trial. All 16 patients were evaluated for safety, and 13 patients were evaluated for efficacy.
The combination demonstrated favorable safety and tolerability. There were no Grade 4 events in the 16 patients studied, and 12.5% experienced Grade 3 IR-AEs, compared to 37% Grade 3/4 IR-AEs reported with nivolumab + ipilimumab in SCLC. ORR was 50% for the six patients receiving the triple IO combination as second line therapy after platinum. Three patients had partial responses (PR), with best tumor reduction at target lesions of 100%, 53% and 45%, respectively. ORR was 43% for the seven patients receiving the triple IO combination as third line therapy, who had either failed or had not responded to platinum and PD-1/PD-L1 inhibitors. Three patients had PRs, with best tumor reductions at target lesions of 78%, 75% and 52%, respectively. Duration of therapy for these 3 PR patients was 18 months, five months (still on treatment) and three months, respectively.
Headquartered in New York City, BeyondSpring is a global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have high unmet medical needs. BeyondSpring’s first-in-class lead asset plinabulin, is being developed as a “pipeline in a drug.” It is filed for approval and has received Priority Review in the U.S. and China for the prevention of chemotherapy-induced neutropenia (CIN) with a PDUFA date of November 30, 2021 in the U.S., and recently announced positive data from the Phase 3 pivotal study (DUBLIN-3) to test an anti-cancer benefit which met overall survival primary endpoint in NSCLC. Additionally, it is being broadly studied in combination with various immuno-oncology regimens that could boost the effects of PD-1 / PD-L1 antibodies. In addition to plinabulin, BeyondSpring’s extensive pipeline includes three pre-clinical immuno-oncology assets and a subsidiary, SEED Therapeutics, which is leveraging a proprietary targeted protein degradation drug discovery platform.
Cautionary Note Regarding Forward-Looking Statements
This press release includes forward-looking statements that are not historical facts. Words such as “will,” “expect,” “anticipate,” “plan,” “believe,” “design,” “may,” “future,” “estimate,” “predict,” “objective,” “goal,” or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company’s future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet our expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSpring’s most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law.
Ashley R. Robinson
LifeSci Advisors, LLC
Darren Opland, Ph.D.