AbbVie , a global biopharmaceutical company, announced preliminary data from the ongoing Phase 1/2b PCYC-1119 trial suggesting that the combination of ibrutinib (IMBRUVICA®) plus carfilzomib with or without dexamethasone was well tolerated in relapsed or refractory patients with multiple myeloma (MM), with an initial objective response rate (ORR) of 62%. These data will be presented today in an oral presentation at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL at 5:30 p.m. ET. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie Company, and Janssen Biotech, Inc.
MM is a blood cancer that most commonly arises from B cells, a type of white blood cell (lymphocyte) that originates in the bone marrow. This year, approximately 26,850 people will be diagnosed with the disease and about 11,240 will die.1
“Multiple myeloma can be a very difficult form of cancer to treat and many patients eventually relapse or become resistant to treatment with standard therapies,” said Ajai Chari, M.D., Associate Professor of Medicine and Director of Clinical Research in the Multiple Myeloma Program at the Icahn School of Medicine at Mount Sinai, New York, NY, and lead study investigator.* “These initial data are encouraging as they suggest the combination of ibrutinib plus carfilzomib and dexamethasone has promising clinical potential, particularly in the primarily refractory patient population who participated in this study.”
Thirty-nine patients were evaluable for efficacy and demonstrated a 62% ORR during early follow-up, with a clinical benefit rate (CBR) of 72%. Overall, the combination was well tolerated, with no dose- limiting toxicities observed during the dose escalation phase.
“As we continue to investigate the use of ibrutinib across a number of hematologic malignancies, multiple myeloma remains an area of great clinical need,” said Thorsten Graef, M.D., Ph.D., Head of Hematology & Global Medical Safety at Pharmacyclics. “Many of these patients eventually relapse when treated with other traditional therapies, so new options are greatly needed. We are hopeful ibrutinib may help answer the call for new alternatives and look forward to continuing to follow its promising progress for the treatment of this disease.”
The ongoing, multicenter, dose-escalation Phase 1/2b study evaluated the safety and efficacy of ibrutinib in combination with carfilzomib with or without dexamethasone in 40 relapsed or refractory MM patients. Patients received the combination across multiple dose levels during the Phase 1 portion, with no dose-limiting toxicities observed. Cohorts 2b (n=14; ibrutinib 560mg once daily plus carfilzomib and dexamethasone) and 3b (n=18; ibrutinib 840mg once daily plus carfilzomib and dexamethasone) was determined to be the recommended Phase 2 dose to further assess the safety and efficacy of the combination. In cohort 3b, the ORR was 65% and the CBR was 76%, including three very good partial responses and one stringent complete response.
The most common all grade non-hematologic adverse events (AEs in ≥20% of patients) across all cohorts in this study were diarrhea, constipation, fatigue, cough and nausea. Grade 3 or greater hematologic AEs (≥10% of patients) included hypertension, anemia, pneumonia, thrombocytopenia, diarrhea and fatigue. In addition, 12 patients discontinued treatment due to progressive disease, eight discontinued due to an AE and nine discontinued due to investigator or patient decision.
IMBRUVICA is currently approved for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients who have del 17p and patients with Waldenström’s macroglobulinemia.2 IMBRUVICA is also approved for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.2
IMBRUVICA is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK).2 IMBRUVICA was one of the first medicines to receive a U.S. FDA approval after being granted a Breakthrough Therapy Designation, and IMBRUVICA is one of the few therapies to receive three separate designations.
BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.2,3 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.2
IMBRUVICA is being studied alone and in combination with other treatments in several blood cancers. More than 6,100 patients have been treated in clinical trials of IMBRUVICA conducted in 35 countries by more than 800 investigators. Currently, 16 Phase 3 trials have been initiated with IMBRUVICA and 67 trials are registered on www.clinicaltrials.gov.
INDICATIONS IMBRUVICA is indicated to treat people with:
- Chronic lymphocytic leukemia (CLL) who have received at least one prior therapy
- Chronic lymphocytic leukemia (CLL) with 17p deletion Waldenström’s macroglobulinemia
- Mantle cell lymphoma (MCL) who have received at least one prior therapy – accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
- Patients taking IMBRUVICA for CLL or WM should take 420 mg taken orally once daily (or three 140 mg capsules once daily).
- Patients taking IMBRUVICA for MCL should take 560 mg taken orally once daily (or four 140 mg capsules once daily).
- Capsules should be swallowed whole with a glass of water. Do not open, break or chew the capsules.