Trial Drug for CIN Demonstrates Positive Results for Chemotherapy Optimization

A phase 2 drug trial for treatment of chemotherapy-induced neutropenia (CIN) has demonstrated positive results.¹

The PROTECTIVE-2 (Study 106) superiority trial found that a marine-derived small-molecule (Plinabulin, BeyondSpring) under development as an anticancer therapy improved dose and regiment compliance of the chemotherapy combination of docetaxel, doxorubicin, and cyclophosphamide (TAC) when combined with pegfilgrastim (Neulasta, Amgen), compared with compliance of TAC with pegfilgrastim alone.¹

Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) and the standard of care for CIN.¹

The investigational, marine-derived small-molecule binds to and affects the function of the protein tubulin within cells of the body, and the drug has demonstrated to differ significantly from other approved or advanced tubulin targeting agents, according to BeyondSpring. Clinical and nonclinical testing has demonstrated a positive effect of this investigational drug on CIN, a major source of chemotherapy dose reductions and toxicity.²

PROTECTIVE-2 evaluated superiority potential in the prevention of CIN in patients with breast cancer. Those studied were treated with TAC with 20 mg/m² of the investigational drug combined with 6 mg of pegfilgrastim (n=16) compared with 6 mg of pegfilgrastim alone (n=22).¹

According to BeyondSpring, the investigational drug + G-CSF improves compliance with targeted chemotherapy. The study found:¹

• Dose reduction (over 15%) 6.3% of patients in the combination arm versus 22.7% in pegfilgrastim arm. A chemotherapy dose reduction of more than 15% leads to a 50% survival reduction.
• Downgraded regimen (from TAC to TC) No (0%) patients in the combination arm downgraded chemotherapy from the TAC regimen to the TC regimen versus 18.2% in the pegfilgrastim arm. TAC with an objective response rate (ORR) at 83% is a more effective chemotherapy regimen than TC with an ORR at 42%.

“Clinical research demonstrates that patients who receive over 85% of the optimal chemotherapy dose on time have significantly better overall survival,” said Lan Huang, PhD, BeyondSpring’s CEO and co-founder, in a prepared statement. "Additionally, monotherapy G-CSF has been shown to help some patients maintain chemotherapy regimens.”¹

However, an analysis of more than 16,000 patients with monotherapy G-CSF showed that few patients were able to maintain their targeted regimen, according to Huang.¹

Grade 4 neutropenia occurs in as many as 52% of patients who are undergoing high-risk chemotherapy, even with G-CSF treatment, and is the primary reason for changes in chemotherapy regimens, such as decreasing, delaying, downgrading or discontinuing chemotherapy treatment.¹

Ramon Mohanlal, MD, PhD, BeyondSpring’s chief medical officer and executive vice president, Research and Development, said the ability to reduce grade 4 neutropenia means that oncologists can optimize cancer patients’ chemotherapy regimens with stable doses, sustained cycles, and the strongest regimens.¹

“This approach provides potential benefits for both clinicians and patients: clinicians may gain greater control over cancer care, and patients may experience better clinical outcomes and an improved quality of life,” Mohanla said in a prepared statement.¹

“The improvement in the prevention of grade 4 neutropenia that is seen with the Plinabulin-Neulasta combination is even more important in today’s health care environment due to the devastating impact of [the coronavirus disease 2019] COVID-19 on immune-suppressed patients. We look forward to the upcoming phase 3 interim topline data readout for PROTECTIVE-2, which represents an important milestone to potentially serve as a new standard of care in CIN treatment,” Mohanial said.¹

The drug also is under investigation for treatment of non-small cell lung cancer.^1,2

REFERENCES

• BeyondSpring’s PROTECTIVE-2 (Study 106) Phase 2 Trial for Chemotherapy-Induced Neutropenia Shows Positive Results in Chemotherapy Optimization with Potentially Better Clinical Outcomes [news release]. New York, NY; June 9, 2020: BeyondSpring [email]. Accessed June 9, 2020.
• Beyond Spring. Plinabulin. Beyond Spring website. https://www.beyondspringpharma.com/ChannelPage/index.aspx Accessed June 9, 2020.