On February 14, 2019 Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), a biopharmaceutical company focused on developing and commercializing medicines seeking to improve the survival and quality of life of cancer patients, reported that the results of the Phase 2 DYNAMO study, which evaluated COPIKTRA (duvelisib) capsules in patients with indolent non-Hodgkin lymphoma (iNHL) who were refractory to both rituximab and chemotherapy or radioimmunotherapy, was published online in the [peer-reviewed] Journal of Clinical Oncology (Press release, Verastem, FEB 14, 2019, View Source;p=RssLanding&cat=news&id=2387473 [SID1234533319]). COPIKTRA received accelerated approval from the U.S. Food and Drug Administration on September 24, 2018 for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. Additionally, COPIKTRA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) after at least two prior therapies.
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COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), a dual inhibitor of both PI3K-delta and PI3K-gamma. The COPIKTRA New Drug Application (NDA) was supported by clinical data from the open-label, single-arm Phase 2 DYNAMO study (NCT01882803), which evaluated the efficacy and safety of COPIKTRA (25mg twice daily) as a monotherapy in 129 adult patients with various types of iNHL, including follicular lymphoma (FL; n=83), small lymphocytic lymphoma (SLL; n=28) or marginal zone lymphoma (MZL; n=18), whose disease had progressed and who were refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint of the study was ORR as assessed by an independent review committee (IRC).
"Indolent non-Hodgkin lymphoma remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies," said Ian Flinn, M.D., Ph.D., Director of the Lymphoma Research Program at Sarah Cannon Research Institute, lead investigator of the Phase 2 DYNAMO study and lead author of the manuscript. "In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, including in patients with SLL, FL and MZL. Duvelisib is an important addition to the evolving treatment paradigm for patients with FL and we are delighted to have the study results published in this prestigious journal to share with the medical and scientific communities."
While MZL patients were included in the DYNAMO study, COPIKTRA has not been deemed safe and effective by the FDA for use in treating patients suffering from MZL, however, MZL represents a potential new patient indication that may benefit from COPIKTRA.
The National Comprehensive Cancer Network (NCCN) has added COPIKTRA to the Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL, FL and MZL. The NCCN Guidelines are the standard physician resource for determining the appropriate course of treatment for patients.
The full manuscript, titled "DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma," (Flinn, et al. DOI: 10.1200/JCO.18.00915) can be accessed here.
Results of the Phase 2 DYNAMO Study in iNHL
The ORR per IRC-assessed response was 47% (95% CI, 38% to 56%). The study met its primary end point (p<0.001). ORR per IRC was 42%, 68%, and 39% in FL, SLL, and MZL subtypes, respectively. Responses were rapid and durable. Median time to response (TTR) was 1.87 months (range, 1.4 to 11.7 months), with 59% and 84% of patients responding by 2 and 4 months, respectively. Median duration of response (DOR) was 10 months (95% CI, 6.5 to 10.5 months), with estimated probabilities of remaining in response at 6 and 12 months of 69% and 35%. Median PFS was 9.5 months (95% CI, 8.1 to 11.8 months), with the probability of surviving and being progression free at 6 months estimated at 62%. Median overall survival (OS) was 28.9 months (95% CI, 21.4 months to not estimable), and OS at 1 year was estimated at 77%. Among the 39 patients with FL who received an R-CHOP (or equivalent) chemoimmunotherapy regimen as first therapy, 30 (77%) experienced early relapse (no response during treatment or progressive disease or time to next treatment less than 2 years). This patient subgroup showed an ORR of 33%, median DOR of 12.6 months and median PFS of 8.2 months. The approval and corresponding label of COPIKTRA in FL was based on the efficacy and safety results from the FL patients (n=83) in DYNAMO that had received at least two prior systemic therapies. The accelerated approval was based on overall response rate (ORR) and continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. COPIKTRA is not FDA approved for MZL.
COPIKTRA contains a BOXED WARNING for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. More information about these Boxed Warnings and additional Important Safety Information can be found below and in the full Prescribing Information at www.COPIKTRA.com.Verastem Oncology is implementing a Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on COPIKTRA.
COPIKTRA is associated with adverse reactions which may require dose reduction, treatment delay or discontinuation of COPIKTRA. In addition to the BOXED WARNING, COPIKTRA has WARNINGS AND PRECAUTIONS for hepatotoxicity, neutropenia, and embryo-fetal toxicity. The most common ADVERSE REACTIONS (reported in ≥ 20% of patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.
Please see important Safety Information provided below and Prescribing Information including BOXED WARNING and Medication Guide at www.COPIKTRAHCP.com/prescribinginformation
About Follicular Lymphoma
Follicular lymphoma (FL) is typically a slow-growing or indolent form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes, making it a B-cell lymphoma. This lymphoma subtype accounts for 20 to 30 percent of all NHL cases, with more than 140,000 people in the US with FL and more than 13,000 newly diagnosed patients this year. Common symptoms of FL include enlargement of the lymph nodes in the neck, underarms, abdomen, or groin, as well as fatigue, shortness of breath, night sweats, and weight loss. Often, patients with FL have no obvious symptoms of the disease at diagnosis. Follicular lymphoma is usually not considered to be curable, but more of a chronic disease, with patients living for many years with this form of lymphoma. The potential of additional oral agents, particularly as a monotherapy that can be used in the general community physician’s armamentarium, may hold significant value in the treatment of patients with FL.
About COPIKTRA (duvelisib)
COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies and relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. COPIKTRA is also being developed by Verastem Oncology for the treatment of peripheral T-cell lymphoma (PTCL), for which it has received Fast Track status, and is being investigated in combination with other agents through investigator-sponsored studies.4 For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.