Eflapegrastim (Rolontis), a novel long-acting granulocyte-colony stimulating factor, has met its primary endpoint of non-inferiority in duration of severe chemotherapy-induced neutropenia in comparison with pegfilgrastim (Neulasta) in the phase III ADVANCE study, according to Spectrum Pharmaceuticals, Inc., the biotechnology company developing the agent.
Lee S. Schwartzberg, MD, FACP
Eflapegrastim (Rolontis), a novel long-acting granulocyte-colony stimulating factor (G-CSF), has met its primary endpoint of non-inferiority in duration of severe chemotherapy-induced neutropenia in comparison with pegfilgrastim (Neulasta) in the phase III ADVANCE study, according to Spectrum Pharmaceuticals, Inc., the biotechnology company developing the agent.
The company has completed enrollment of an additional phase III study, RECOVER, and plans to file a biologics license application (BLA) with the FDA for eflapegrastim in the fourth quarter of this year.
“The ADVANCE study affirms the efficacy and safety of Rolontis that was observed in the phase II study," said Lee S. Schwartzberg, MD, FACP, professor of medicine and division chief, hematology oncology, The University of Tennessee Health Science Center, and executive director, UT/West Cancer Center, in a statement. “If approved, this drug would be a welcome addition to supportive care treatment options for patients [with cancer] receiving myelosuppressive cytotoxic chemotherapy.”
Using a proprietary long-acting protein/peptide discovery technology, LAPSCOVERY, eflapegrastim binds to the G-CSF receptor expressed on granulocyte progenitors and stimulates their proliferation and subsequent maturation to functionally active neutrophils.
Spectrum launched the phase III ADVANCE study in accordance with the FDA Special Protocol Assessment after a successful phase II dose-finding study showed acceptable safety and efficacy profile for eflapegrastim.
The randomized, multicenter, active-controlled ADVANCE trial enrolled 406 patients with early-stage breast cancer who received docetaxel and cyclophosphamide (TC) chemotherapy every 21 days. Patients were randomized 1:1 to treatment with eflapegrastim or pegfilgrastim. The primary endpoint was the duration of severe neutropenia (absolute neutrophil counts [ANC] <0.5×109/L) in cycle 1 of chemotherapy, based on central laboratory assessment of ANC over the cycle. Key secondary endpoints included time to ANC recovery, depth of ANC nadir, and incidence of febrile neutropenia in cycle 1.
To be eligible for inclusion on the study, patients had to be ≥18 years of age, have a new diagnosis of histologically confirmed early-stage breast cancer, defined as operable stage I to stage IIIa breast cancer; be a candidate to receive adjuvant or neoadjuvant TC chemotherapy; have adequate hematologic, renal, and hepatic function; and have an ECOG performance status of ≤2. Patients were excluded for the study if they had an active concurrent malignancy or a life-threatening disease, locally recurrent/metastatic or contralateral breast cancer, prior hematopoietic stem cell transplant or radiation therapy, or previous exposure to filgastrim, pegfilgrastim, or other G-CSF products prior to the administration of eflapegrastim.
Eflapegrastim was administered in prefilled single-use syringes at a fixed dose of 13.2 mg/0.6 mL for subcutaneous injection on day 2 of each cycle. Pegfilgrastim was given as a single-dose subcutaneous injection of 6 mg/0.6 mL on day 2 of each cycle.
Spectrum has also announced that the incidence of adverse events was similar in the eflapegrastim and pegfilgrastim arms.
"The positive top-line data from our phase III study is an important milestone for Spectrum as we continue to move our company forward,” said Joe Turgeon, president and chief executive officer of Spectrum Pharmaceuticals. "Also, the completion of enrollment of our second phase III, the RECOVER study, keeps us on track to file a BLA in the fourth quarter of 2018. Rolontis has the potential to be an important alternative for physicians and patients within this multibillion dollar market.”
Schwartzberg L S, Peguero J A, Vacirca J L, et al. Randomized Phase 3 Study of ROLONTIS (Eflapegrastim), a Novel Long-acting G-CSF, Versus Neulasta (Pegfilgrastim) in the Management of Chemotherapy-Induced Neutropenia in Early-Stage Breast Cancer Patients Receiving Docetaxel and Cyclophosphamide (TC) (ADVANCE Study). Poster presented at: San Antonio Breast Cancer Symposium, December 6-10, 2016. San Antonio, TX. Abstract OT1-01-11.