Phase 2 Single-Arm BLAST Study Shows Median Overall Survival of 36.5 Months in Patients With Minimal Residual Disease-Positive Acute Lymphoblastic Leukemia

More Than Half of Patients who Achieved an MRD-Negative Complete Response Still Alive at Five Years

Only CD19-Targeted Immuno-oncology Therapy With Five-Year Survival Data

THOUSAND OAKS, CA, USA I June 15, 2019 I Amgen (NASDAQ:AMGN) today announced the five-year overall survival (OS) analysis from the single-arm, Phase 2 BLAST study that evaluated BLINCYTO® (blinatumomab) in patients with minimal residual disease (MRD)-positive acute lymphoblastic leukemia (ALL). The study found that with a median follow-up of 59.8 months, the median OS for BLINCYTO-treated patients was 36.5 months (95 percent CI: 22 months – not estimable [NE]). More than half of patients who achieved a complete MRD response following the first cycle of BLINCYTO treatment were alive at five years. These results from the largest prospective trial ever conducted in MRD-positive ALL were presented today during an oral presentation at the 24th Annual Congress of the European Hematology Association (EHA) in Amsterdam.

“As the only CD19-targeted immuno-oncology therapy with five-year survival data, BLINCYTO continues to demonstrate compelling results for ALL patients,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “We are proud of the science behind our BiTE® technology. These data in an MRD-positive ALL patient population give us increased confidence in the clinical benefit of BLINCYTO, especially when these patients are treated earlier.”

The Phase 2 open-label BLAST study enrolled 116 patients with MRD-positive Philadelphia chromosome-negative (Ph-) B-cell precursor ALL in first or subsequent complete hematologic remission after at least three intensive chemotherapy blocks of treatment. Of the 116 enrolled patients, OS was evaluated for 110 patients with less than five percent leukemic blasts, including 74 patients who received hematopoietic stem cell transplantation (HSCT) in continuous complete remission (CCR) after BLINCYTO treatment.

Results presented at EHA showed that in 84 patients who achieved a complete MRD response (had no measurable MRD), median OS was not reached (95 percent CI: 29.5 months – NE) compared to 14.4 months for those who had measurable MRD (n=23; 95 percent CI: 3.8 – 32.3 months). Among patients with MRD in first complete remission (CR1), median OS was not reached for those who achieved a complete MRD response (95 percent CI: 29.5 months – NE) versus 10.6 months (95 percent CI: 2.7 – 39.7 months) for those who did not achieve complete MRD response (n=13; p=0.008).

“The presence of MRD is a strong predictor of relapse in patients with B-cell precursor ALL,” said Nicola Gökbuget, M.D., principal investigator for the BLAST study and head of the German Multicenter Study Group for Adult ALL in Frankfurt, Germany. “Results from the final follow-up of the BLAST trial at five years demonstrate that early achievement of complete molecular remission with BLINCYTO is associated with prolonged survival.”

Safety results among MRD-positive patients were consistent with the known safety profile of BLINCYTO.  

MRD refers to the presence of cancer cells that remain detectable, despite a patient having achieved complete remission by conventional assessment.1 The presence of MRD is broadly considered the most important independent prognostic factor in ALL.2-8 MRD is only measurable through the use of highly sensitive testing methods that detect cancer cells in the bone marrow with a sensitivity of at least one cancer cell in 10,000 cells – versus about one in 20 with a conventional microscope-based evaluation.1,9,10

BLINCYTO, a bispecific CD19-directed CD3 T cell BiTE® (bispecific T cell engager) molecule, is the first approved molecule from Amgen’s BiTE immuno-oncology platform, and the first and only therapy to receive regulatory approval globally for the treatment of MRD. 

About the BLAST Study
The BLAST study is the largest prospective trial in patients with MRD-positive ALL. It is an open-label, multicenter, single-arm, Phase 2 study that evaluated the efficacy, safety and tolerability of BLINCYTO in adult patients with MRD-positive B-cell precursor ALL in complete hematologic remission after three or more cycles of intensive chemotherapy. Patients received continuous intravenous infusion of BLINCYTO 15 μg/m2/d for four weeks, followed by two weeks off. Patients received up to four cycles of treatment and could undergo HSCT at any time after the first cycle, if eligible. Efficacy was based on achievement of undetectable MRD within one cycle of BLINCYTO treatment and hematological relapse-free survival (RFS). Results from the primary analysis BLAST study were presented at the 57th American Society of Hematology (ASH) Annual Meeting & Exposition in 2015 and published in Blood in 2018. Additional secondary endpoints included incidence and severity of adverse events, OS, time to hematological remission and duration of complete MRD response. Survival follow-up visits for assessment of hematological RFS and OS took place every six months until completion of a five-year period after treatment start with BLINCYTO. Three-year OS data results from the BLAST study were also featured in an oral presentation during the 60th ASH Annual Meeting & Exposition on Dec. 3, 2018.

About ALL and MRD
ALL is a rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children.11,12 Poor outcomes have been observed in patients who achieve first or second complete hematologic remission but are persistently MRD-positive, which currently remains detectable at the molecular level after treatment.1,8 For more information about MRD, please visit AmgenOncology.com.   

About BiTE Technology
BiTE (Bispecific T cell engager) technology is a targeted immuno-oncology platform that is designed to engage patients’ own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells with the goal of eliminating detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has the goal of off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of solid and hematologic malignancies, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential.

About BLINCYTO® (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell BiTE (bispecific T cell engager), immunotherapy that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of effector T cells. BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration in 2014, and carries full approval in the U.S. for the treatment of relapsed or refractory B-cell precursor ALL in adults and children. In the U.S., BLINCYTO is also approved for the treatment of adults and children with B-cell precursor ALL in first or second complete remission with MRD greater than or equal to 0.1 percent. This indication is approved under accelerated approval based on MRD response rate and hematological RFS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In the European Union (EU), BLINCYTO is indicated for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor ALL and for the treatment of Ph- CD19-positive B-cell precursor ALL in first or second complete remission with MRD greater than or equal to 0.1 percent.

BLINCYTO is now approved in 57 countries, including all member countries in the EU and European Economic Area, Canada, Japan and Australia.

About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.   

For more information, follow us on www.twitter.com/amgenoncology.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

References:

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  9. Gökbuget N, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120:1868-1876.
  10. Brüggemann M, et al. Has MRD monitoring superseded other prognostic factors in adult ALL? Blood. 2012;120:4470-4481.
  11. Cancer Research UK. About acute lymphoblastic leukaemia (ALL). http://www.cancerresearchuk.org/about-cancer/acute-lymphoblastic-leukaemia-all/about. Accessed June 10, 2019. 
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SOURCE: Amgen