– First Presentation of Interim Phase 1/2 Data Reported in Pediatric Patients with Relapsed or Refractory Hodgkin Lymphoma or relapsed or refractory Systemic Anaplastic Large Cell Lymphoma –
Chicago, IL., June 1, 2013 and Osaka, Japan, June 3, 2013 – Takeda Pharmaceutical Company Limited (TSE:4502) today announced interim data from a Phase 1/2, open-label, multicenter study with ADCETRIS® (brentuximab vedotin) in pediatric patients diagnosed with CD30-positive relapsed or refractory Hodgkin lymphoma (HL) or relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). Data were presented from the Phase 1 portion of the study, which evaluated the safety, maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and pharmacokinetics (PK) of ADCETRIS. The results were reported during a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting held May 31 – June 4, 2013 in Chicago, IL.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and sALCL.
“This is the first clinical trial examining the use of ADCETRIS in pediatric patients,” said Kathleen Neville, M.D., M.S., Director, Experimental Therapeutics in Pediatric Cancer, Children’s Mercy Hospitals and Clinics, Kansas City, MO. “There is an unmet medical need for children diagnosed with relapsed or refractory HL or relapsed or refractory sALCL. We are encouraged by these early results and look forward to reporting data from the Phase 2 portion of the study when they are available.”
Phase I/II Study of Brentuximab Vedotin in Pediatric Patients with Relapsed or Refractory Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Interim Phase I Safety Data
The poster presentation featured interim data from the Phase 1 portion of the study, which evaluated 12 pediatric patients aged 2 to <18 years with relapsed or refractory HL or relapsed or refractory sALCL. The primary endpoints were safety, pediatric MTD and/or RP2D and PK. The secondary endpoint that was reported included overall response rate (ORR) (complete remission (CR) + partial remission (PR)) per Independent Review Facility (IRF) assessment.
Data, presented by Anna R.K. Franklin, M.D., Children's Cancer Hospital, MD Anderson Cancer Center, Houston, TX., included:
- The RP2D for pediatric patients was determined to be 1.8 milligrams/kilogram (mg/kg) on an every three week basis
- The most common treatment-emergent adverse events (TEAEs) ≥ Grade 2 were nausea (8 patients), pyrexia (6 patients), upper abdominal pain (4 patients) and paresthesia (4 patients)
- Seven serious AEs (SAEs) of ≥ Grade 3 were reported in 6 patients (50 percent) at 1.8 mg/kg, including pyrexia unrelated to treatment (1 patient), hepatotoxicity and febrile neutropenia (1 patient), anaphylactic reaction (1 patient), supraventricular tachycardia unrelated to treatment (1 patient), pain in extremity (1 patient), and cardiac arrest resulting in death unrelated to treatment (1 patient)
- Two patients who received 1.8 mg/kg of ADCETRIS discontinued treatment due to a drug-related SAE
- PK analyses showed dose-dependent exposure and MMAE release time typical of ADCs
- The ORR of 8 evaluable patients who received the RP2D was 88 percent; the CR rate was 38 percent
The median age of the patients was 14.5 years. Ten patients were diagnosed with relapsed or refractory HL and two patients were diagnosed with relapsed or refractory sALCL. Participants received a median of 7 cycles (range, 1–14) of ADCETRIS by intravenous infusion once every 21 days starting with 1.4 mg/kg escalating to 1.8 mg/kg.
Details of the poster presentation are as follows:
- Poster session on June 1, 2013 at 1:15 PM CT
- Poster discussion on June 1, 2013 from 4:45 PM – 5:45 PM CT in Hall S A2
- Poster: #36C
- First author: Kathleen Neville, M.D., Children’s Mercy Hospital Hematology/Oncology, Kansas City, MO
This clinical trial is part of the Pediatric Investigational Plan approved by the Pediatric Committee of the European Medicines Agency. The Phase 2 portion of the study is ongoing and results will be presented at a later date. For more information about the trial please visit www.clinicaltrials.gov.
About ADCETRIS® (brentuximab vedotin)
ADCETRIS® (brentuximab vedotin) is the first and only targeted CD30 antibody-drug conjugate (ADC) being evaluated in a variety of CD30-expressing malignancies including Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). The ADC utilizes Seattle Genetics’ proprietary technology, which employs a linker system designed to be stable in the bloodstream but to release monomethyl auristatin E (MMAE) upon internalization into CD30-expressing tumor cells.
ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for the treatment of adult patients with relapsed or refractory CD30-positive HL: (1) following autologous stem cell transplant (ASCT), or (2) following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS also received marketing authorization by regulatory authorities in Switzerland and Korea.
ADCETRIS was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2011 for two indications: (1) the treatment of patients with HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.
Millennium: The Takeda Oncology Company and Seattle Genetics are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group is solely responsible for development costs.
About Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.
About Anaplastic Large Cell Lymphoma
ALCL is a type of aggressive T-cell lymphoma, comprising about 3 percent of all non-Hodgkin lymphomas (NHL) in adults and between 10 and 30 percent of all NHL in children. There are two distinct forms/types of ALCL, including primary cutaneous ALCL and systemic ALCL (sALCL). sALCL is a clinically aggressive, systemic lymphoma that primarily involves lymph nodes.
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for people worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
- Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Treating physicians should monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
- Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be immediately and permanently discontinued and appropriate medical management instituted.
- Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation. Prolonged (≥1 week) severe neutropenia can occur with ADCETRIS.
- Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these patients should be monitored closely and appropriate measures taken.
- Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
- Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer appropriate medical therapy.
- Use in pregnancy: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus.
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.ADCETRIS.com.
Editor’s Note: This press release is also available under the Media section of the Company’s website at: www.millennium.com/InTheNews.aspx.
Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)