- Based on the observation of no dose limiting toxicities (DLT) on the Day 1-5 schedule, 1000 mg/m2 was determined as the maximum tolerated dose (MTD) for BELEODAQ® (belinostat).
- ORR was 86% with CR 71% in the Cohort treated at the MTD (1000 mg/m2 for 5 days).
EAST WINDSOR, N.J.–(BUSINESS WIRE)–Acrotech Biopharma, LLC a commercial-stage biopharmaceutical company focused on commercializing and developing novel products, with an initial focus on hematologic malignancies, today announced the publication of data from a phase 1 study of BELEODAQ® (belinostat) combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in adult patients with peripheral t-cell lymphoma in the journal Experimental Hematology and Oncology.
In the study, a total of 23 adult patients with histologically confirmed, previously untreated PTCL were treated with BELEODAQ® in combination with standard CHOP for six cycles with varying schedules.
The primary objective of this study was to determine the maximum tolerated dose (MTD) of BELEODAQ® combined with CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall response rate (ORR), and BELEODAQ® pharmacokinetics (PK).
This was a two-part study and in Part A, a traditional 3 + 3 dose-escalation schema was implemented, in which 2 sequential dose schedule cohorts were enrolled to determine the MTD of Bel-CHOP. The initial cohort (Cohort 3, n=8) received BELEODAQ® on Days 1–3 of every cycle and after only 1 of 8 patients (13%) experienced DLTs, the study was escalated to Cohort 5 (n=3) receiving 1000 mg/m2 BELEODAQ® administered on Days 1–5. As no DLTs were observed in Cohort 5, the BELEODAQ® Day 1-5 schedule, 1000 mg/m2 was determined as the MTD. In Part B, the MTD determined in Part A, was evaluated in 12 additional patients to further define safety and tolerability and establish the recommended dose of BELEODAQ® in the Bel-CHOP regimen.
In 18 of the 21 evaluable patients who completed 6 cycles of Bel-CHOP, the ORR was 86% with a 71% complete response (CR) in the Cohort 5 + expansion patients treated at the MTD (1000 mg/m2 for 5 days). The ORR was similar across age groups, tumor subtypes, or if bone marrow lymphoma involvement or not. In particular, the ORR in AITL patients was 89% and it was 90% in patients with bone marrow involvement.
All patients experienced adverse events including nausea (78%), fatigue (61%), and vomiting (57%). The most frequently reported Grade 3 or 4 adverse events were hematological in nature, consistent with reported AEs observed with cytotoxic therapy. Serious adverse events (SAEs) occurred in 43% of patients. SAEs included febrile neutropenia (17%), pyrexia (13%), and nausea and neutropenia (each 9%), all of which were considered related to Bel-CHOP study treatment. There were no deaths attributable to Bel-CHOP study treatment toxicity. One patient died due to respiratory failure secondary to disease progression.
“In this study, the combination of BELEODAQ® and CHOP was well tolerated and induced a high percentage of clinical responses when administered as first-line therapy in patients with newly diagnosed PTCL. The optimal dose of BELEODAQ® in the Bel-CHOP regimen was equivalent to the single-agent dose and schedule. The type and severity of adverse events we observed were similar to what we would expect from CHOP alone,” said Patrick B Johnston, MD, PhD of the Mayo Clinic, lead investigator of the study.
“PTCL is a very aggressive disease and patients will benefit from the continued development of effective treatment options. We are very encouraged with the results from our Phase 1 trial. The study has furthered our understanding of this disease and will help us strategize on how to best continue the development of BELEODAQ for patients with PTCL,” said Dr. Ashish Anvekar, President Acrotech Biopharma.
BELEODAQ in combination with CHOP is not approved for use in any region.
About BELEODAQ®
BELEODAQ® is a histone deacetylase inhibitor indicated for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
Important Safety Information
WARNINGS AND PRECAUTIONS
Hematologic Toxicity: BELEODAQ can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and/or anemia; monitor blood counts weekly during treatment, and modify dosage as necessary.
Infections: Serious and sometimes fatal infections, including pneumonia and sepsis, have occurred with BELEODAQ. Do not administer BELEODAQ to patients with an active infection. Patients with a history of extensive or intensive chemotherapy may be at higher risk of life threatening infections.
Hepatotoxicity: BELEODAQ can cause fatal hepatotoxicity and liver function test abnormalities. Monitor liver function tests before treatment and before the start of each cycle. Interrupt or adjust dosage until recovery, or permanently discontinue BELEODAQ based on the severity of the hepatic toxicity.
Tumor Lysis Syndrome: Tumor lysis syndrome has occurred in BELEODAQ-treated patients in the clinical trial of patients with relapsed or refractory PTCL. Monitor patients with advanced stage disease and/or high tumor burden and take appropriate precautions.
Gastrointestinal Toxicity: Nausea, vomiting and diarrhea occur with BELEODAQ and may require the use of antiemetic and antidiarrheal medications.
Embryo-Fetal Toxicity: Based on its mechanism of action and findings of genotoxicity, BELEODAQ can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with BELEODAQ and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with BELEODAQ and for 3 months after the last dose.
The most common adverse reactions observed in more than 25% of patients with relapsed or refractory PTCL from the original trial, who were treated with BELEODAQ, were nausea (42%), fatigue (37%), pyrexia (35%), anemia (32%), and vomiting (29%). Sixty-one patients (47.3%) experienced serious adverse reactions while taking BELEODAQ or within 30 days after their last dose of BELEODAQ. The most common serious adverse reactions (>2%) were pneumonia, pyrexia, infection, anemia, increased creatinine, thrombocytopenia, and multi-organ failure.
DRUG INTERACTIONS
- Belinostat is primarily metabolized by UGT1A1. Avoid concomitant administration of BELEODAQ with strong inhibitors of UGT1A1
Use in Specific Populations
- Lactation: Due to the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with BELEODAQ and for 2 weeks after the last dose.
- Pregnancy Testing: BELEODAQ can cause fetal harm when administered to a pregnant woman. Pregnancy testing is recommended for females of reproductive potential prior to initiating BELEODAQ.
- Pediatric Use: The safety and effectiveness of BELEODAQ in pediatric patients have not been established
Please see Full Prescribing Information.
About Acrotech Biopharma, LLC.
Acrotech Biopharma LLC, headquartered in East Windsor, New Jersey was founded in 2018. Acrotech was formed as a global platform to commercialize innovative proprietary medications. The company aims to provide scientifically advanced products to address unmet needs and deliver value to patients as well as all healthcare stakeholders. Acrotech aspires to be a patient focused, research-based organization that strives to launch treatments which are accessible to patients that need them. For more information, please visit www.acrotechbiopharma.com.
Contacts
Alberto DeJesus
Acrotech Biopharma
805.427-4733