CAPTIVATE Study Shows an IMBRUVICA® (ibrutinib) Plus VENCLEXTA®/VENCLYXTO® (venetoclax) Chemotherapy-Free Combination Has Potential to Provide Remission After Fixed-Duration Treatment for Chronic Lymphocytic Leukemia (CLL)

- The fixed-duration combination met the primary endpoint of complete response rate at 56% among patients with previously untreated CLL, 70 years old or younger

- At 24 months, progression-free survival was 95% and overall survival (OS) was 98%

- The safety profile of the combination was generally consistent with known adverse events (AEs) for each agent and no new safety signals were identified

- Data to be presented at the virtual American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7501)

NORTH CHICAGO, IL, USA I June 7, 2021 I AbbVie (NYSE: ABBV) today announced new data from the Phase 2 CAPTIVATE (PCYC-1142) study investigating IMBRUVICA® (ibrutinib) in combination with VENCLEXTA®/VENCLYXTO® (venetoclax), an all-oral, once-daily, chemotherapy-free, fixed-duration investigational combination, for patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) during an oral presentation at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7501). The ibrutinib and venetoclax cohort met its primary endpoint of complete response (CR) rate of 56% (95% CI 48-64) among patients without del(17p), 70 years old or younger and with 27.9 months of follow up. This rate was higher than the 37% minimum meaningful rate study assumption (P<0.0001). The CR rate was consistent across all patients in the study including high-risk CLL patient groups. Furthermore, 24-month progression free survival (PFS) and overall survival (OS) were 95% and 98%, respectively. 

"We are encouraged by these promising results, which indicate ibrutinib and venetoclax combined has the potential to serve as an important chemotherapy-free, fixed-duration treatment option for people living with CLL," said Dr. Paolo Ghia, M.D., Ph.D., Professor of Medical Oncology at the Università Vita-Salute San Raffaele and CAPTIVATE steering committee member and investigator.

Ibrutinib plus venetoclax is an investigational fixed-duration combination. Patients received 3 cycles of ibrutinib lead-in followed by 12 cycles of ibrutinib + venetoclax (Ibr 420 mg/day PO; Ven ramp up to 400 mg/day PO). At 27.9 months median duration of follow-up in the fixed-duration cohort, complete response (CR) rate was 56% without del(17p), and CR, including complete response with incomplete marrow recovery (CRi), was 55% in the overall study population and was consistent across high-risk subgroups. Undetectable minimal residual disease (uMRD) was achieved in 77% of patients in peripheral blood and 60% of patients in bone marrow. The most common grade 3/4 adverse effects (AEs) were neutropenia (33%), hypertension (6%) and neutrophil count decreased (5%). AEs led to discontinuation of ibrutinib in 4% and venetoclax in 2% of patients. The safety profile of the combination was generally consistent with known AEs for each agent and no new safety signals were identified.

"Combining our novel therapies to deliver a new potential treatment is an example of AbbVie's innovative approach to identify options for difficult-to-treat blood cancers, like CLL," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development, AbbVie. "We are proud to be leading in the development of this combination to continue raising the standards of care for the blood cancer community."

This data builds on previously reported results from the Minimal Residual Disease (MRD) cohort where undetectable uMRD was achieved in over two-thirds of patients with 12 cycles of ibrutinib plus venetoclax, and 30-month PFS rates were ≥95% irrespective of subsequent randomized treatment (Wierda, ASH 2020).

CAPTIVATE data will also be presented at the European Hematology Association's (EHA) congress taking place from June 9-17, 2021. Additionally, there are other ongoing company-sponsored and investigator-initiated trials exploring the potential of ibrutinib and venetoclax in combination for CLL treatment, including the Phase 3 GLOW study. Results from the ongoing GLOW study, assessing the ibrutinib plus venetoclax combination in comparison to chlorambucil plus obinutuzumab for first-line treatment of patients with CLL or SLL (NCT03462719), will be presented at the upcoming EHA congress.

About CLL
CLL is one of the two most common forms of leukemia in adults and is a type of cancer that can develop from cells in the bone marrow that later mature into certain white blood cells (called lymphocytes).1 While these cancer cells start in the bone marrow, they later spread into the blood. There are approximately 195,129 people with CLL living in the United States with more than 21,000 newly diagnosed patients in 2021.2,3 CLL is predominately a disease of the elderly, with a median age at diagnosis of 70 years and is more common among men than women.4

About the CAPTIVATE Study
The CAPTIVATE study fixed-duration cohort evaluated 159 patients between the ages of 18 and 70 years old with CLL/SLL. Patients received 3 cycles of ibrutinib lead-in followed by 12 cycles of ibrutinib + venetoclax (Ibr 420 mg/day PO; Ven ramp up to 400 mg/day PO). High-risk features included del(17p)/TP53 mutation, 17%; del(11q), 18%; complex karyotype, 19%; and unmutated IGHV, 56%. 147 (92%) and 149 (94%) patients completed planned treatment with ibrutinib and venetoclax respectively. Median time on study was 27.9 month (range, 0.8–33.2). FD cohort primary endpoint was CR rate, including CR with incomplete marrow recovery (CRi) in patients without del(17p). Key secondary endpoints were objective response rate (ORR), duration of response, uMRD rate (<10-4 by 8-color flow cytometry), PFS, OS, tumor lysis syndrome (TLS) risk category reduction based on tumor burden shifted to medium- or low-risk after ibrutinib lead-in therapy and AEs.

The CAPTIVATE study MRD cohort evaluated 164 patients between the ages of 18 and 70 years old with previously untreated CLL/SLL. Patients received 3 cycles of ibrutinib lead-in followed by 12 cycles of ibrutinib + venetoclax (Ibr 420 mg/day PO; Ven ramp-up to 400 mg/day PO). Patients with confirmed uMRD (defined as uMRD serially over ≥3 cycles, and in both PB and BM) after 12 cycles of ibrutinib + venetoclax were randomized 1:1 to receive double-blind treatment with placebo or ibrutinib during a 13th cycle of ibrutinib and venetoclax combined. Patients who did not meet the definition of confirmed uMRD were randomized 1:1 to receive open-label treatment with ibrutinib or continued ibrutinib + venetoclax. Primary endpoint was 1-year DFS rate in the confirmed uMRD patients randomized to placebo vs ibrutinib; DFS was defined as survival without progression or MRD relapse (which was defined as an MRD level of 10-2). Key secondary endpoints were rates of uMRD (<10-4 by 8-color flow cytometry), response per iwCLL, adverse events (AEs), as well as progression-free survival (PFS). The depth of response achieved with this regimen is reflected in the 30-month progression-free survival (PFS) rate of ~95% across all treated patients, including the subset receiving placebo after the fixed-duration treatment. The safety profile of the combination was generally consistent with known adverse events for ibrutinib and venetoclax individually and no new safety signals emerged.

About IMBRUVICA ®  (Ibrutinib)
IMBRUVICA (ibrutinib) is a once-daily, first-in-class BTK inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics, LLC, an AbbVie Company, and Janssen Biotech, Inc. (Janssen). The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.5,6 By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.7

Since its launch in 2013, IMBRUVICA has received 11 FDA approvals across six disease areas: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenström macroglobulinemia; previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* – and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.8

IMBRUVICA is now approved in more than 100 countries and has been used to treat more than 230,000 patients worldwide across its approved indications. IMBRUVICA is the only FDA-approved medicine in WM and cGVHD. IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.

Since 2019, the National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education, recommends ibrutinib (IMBRUVICA®) as a preferred regimen for the initial treatment of CLL/SLL and has Category 1 treatment status for treatment-naïve patients without deletion 17p. In January 2020, the NCCN Guidelines® were updated to elevate IMBRUVICA with or without rituximab from other recommended regimens to a preferred regimen for the treatment of relapsed/refractory MCL, regardless of duration of response to prior chemoimmunotherapy. As of September 2020, the NCCN guidelines were updated to reflect IMBRUVICA with or without rituximab as the only Category 1 preferred regimen for both untreated and previously treated WM patients.

IMBRUVICA® is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit www.IMBRUVICA.com

*Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

Pleaseclick here for full Prescribing Information.

About VENCLEXTA®/VENCLYXTO® (venetoclax)
VENCLEXTA®/VENCLYXTO® (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLXEXTA/VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.
VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood cancers. Venetoclax is approved in more than 80 countries, including the U.S.

The full U.S. prescribing information, including Medication Guide, for VENCLEXTA® can be found here.  

Indication and Important VENCLYXTO® (venetoclax) EU Safety Information10
Indication
 
VENCLYXTO® in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). 

VENCLYXTO® in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy. 

VENCLYXTO® monotherapy is indicated for the treatment of CLL: 

  • In the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
  • In the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor. 

About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.

References:

1 American Society of Hematology. Leukemia. http://www.hematology.org/Patients/Cancers/Leukemia.aspx Accessed May 2021.
2 IMS Database [Data on File].
3 National Cancer Institute. Cancer Stat Facts: Leukemia - Chronic Lymphocytic Leukemia (CLL). https://seer.cancer.gov/statfacts/html/clyl.html. Accessed May 2021.
4 Shanafelt, et al. Age at Diagnosis and the Utility of Prognostic Testing in Patients with Chronic Lymphocytic Leukemia (CLL). Cancer. 2010; 116(20): 4777–4787.
5 Burger JA et al. Leukemia. 2020;34:787-798.
6 Byrd JC et al. N Engl J Med. 2014;371(3):213-223.
5 Genetics Home Reference. Isolated growth hormone deficiency.  http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed November 2020.
6 Turetsky, et al. Single cell imaging of Bruton's Tyrosine Kinase using an irreversible inhibitor. Scientific Reports. volume 4, Article number: 4782 (2014)
7 de Rooij MF, Kuil A, Geest CR, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590-2594.
8 IMBRUVICA U.S. Prescribing Information, April 2020.
9 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.
10 Summary of Product Characteristics for VENCLYXTO (venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG.

SOURCE: AbbVie

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