Data Presented at the 23rd Annual International Congress on Hematologic Malignancies
COPIKTRA Demonstrates Progression-Free Survival of 16.4 Months and an Overall Response Rate of 78% in Adult Patients with CLL/SLL After At Least Two Prior Therapies
BOSTON, MA, USA I March 04, 2019 I 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, today announced a poster highlighting clinical data from the Phase 3 DUO study evaluating COPIKTRA (duvelisib) in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies was presented at the 23rd Annual International Congress on Hematologic Malignancies (ICHM), which took place February 28 – March 3, 2019, in Miami, FL. COPIKTRA, an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, received approval from the U.S. Food and Drug Administration (FDA) for this same indication in September 2018.
COPIKTRA also received accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. The accelerated approval was based on overall response rate and continued approval for this indication may be contingent upon confirmatory trials.
“Although the treatment landscape in CLL/SLL has advanced in recent years, there remains an unmet need with many patients progressing or relapsing,” commented Ian Flinn, MD, PhD, Director, Lymphoma/CLL Program at Sarah Cannon Research Institute and lead investigator of the DUO study. “These data from the randomized Phase 3 DUO study, which were calculated from patients who had previously received at least two prior therapies, demonstrate that COPIKTRA achieved a 78% overall response rate and progression-free survival of 16.4 months, compared to 9.1 months for ofatumumab, in patients with relapsed or refractory CLL/SLL, including in high risk patients with the 17p deletion. With convenient oral administration COPIKTRA has been a valuable addition to the treatment landscape for CLL/SLL patients and for the physicians who treat them.”
Results of the Phase 3 DUO Study Evaluating COPIKTRA in Adult Patients with Relapsed or Refractory CLL/SLL After At Least Two Prior Therapies
The randomized, multicenter, open-label, Phase 3 DUO study, compared COPIKTRA versus ofatumumab in 319 adult patients with CLL (n=312) or SLL (n=7) after at least one prior therapy. The study randomized patients with a 1:1 ratio to receive either COPIKTRA 25mg twice daily until disease progression or unacceptable toxicity, or ofatumumab, an approved standard of care treatment for use in CLL/SLL, for 7 cycles.
The approval of COPIKTRA was based on efficacy and safety analysis of patients with at least 2 prior lines of therapy, where the benefit:risk appeared greater in this more heavily pretreated population compared to the overall trial population.
In this subset (95 randomized to COPIKTRA, 101 to ofatumumab), the median patient age was 69 years (range: 40 to 90 years), 59% were male, and 88% had an ECOG performance status of 0 or 1. Forty-six percent received 2 prior lines of therapy, and 54% received 3 or more prior lines. At baseline, 52% of patients had at least one tumor ≥ 5 cm, and 22% of patients had a documented 17p deletion.
During randomized treatment, the median duration of exposure to COPIKTRA was 13 months (range: 0.2 to 37), with 80% of patients receiving at least 6 months and 52% receiving at least 12 months of COPIKTRA. The median duration of exposure to ofatumumab was 5 months (range: < 0.1 to 6).
Efficacy was based on progression-free survival (PFS) as assessed by an Independent Review Committee (IRC). Other efficacy measures included overall response rate (ORR). Efficacy of COPIKTRA compared to ofatumumab specifically in patients treated with at least two prior therapies is below.
| |
|
|
|
|
|
|
|
|
|
|
|
| Outcome per IRC |
|
|
|
COPIKTRA
N = 95
|
|
|
|
Ofatumumab
N = 101
|
|
|
|
| PFS |
|
|
|
| Number of events, n (%) |
|
|
|
55 (58) |
|
|
|
70 (69) |
|
|
|
| Progressive disease |
|
|
|
44 |
|
|
|
62 |
|
|
|
| Death |
|
|
|
11 |
|
|
|
8 |
|
|
|
| Median PFS (SE), months a |
|
|
|
16.4 (2.1) |
|
|
|
9.1 (0.5) |
|
|
|
|
Hazard Ratio (SE), b
COPIKTRA/ofatumumab
|
|
|
|
0.40 (0.2) |
|
|
|
| Response rate |
|
|
|
| ORR, n (%) c |
|
|
|
74 (78) |
|
|
|
39 (39) |
|
|
|
| CR |
|
|
|
0 (0) |
|
|
|
0 (0) |
|
|
|
| PR |
|
|
|
74 (78) |
|
|
|
39 (39) |
|
|
|
| Difference in ORR, % (SE) |
|
|
|
39 (6.4) |
|
|
|
| |
|
|
|
|
|
|
|
Abbreviations: CR = complete response; IRC = Independent Review Committee; PFS = progression-free survival; PR = partial response; SE = standard error
a Kaplan-Meier estimate
b Standard Error of ln(hazard ratio) = 0.2
c IWCLL or revised IWG response criteria, with modification for treatment-related lymphocytosis
COPIKTRA has a BOXED WARNING for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem Oncology has implemented a Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on COPIKTRA.
Additionally, COPIKTRA is also associated with adverse reactions which may require dose reduction, treatment delay or discontinuation of COPIKTRA. WARNINGS AND PRECAUTIONS are provided for infections, diarrhea or colitis, cutaneous reactions, pneumonitis, 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 the Important Safety Information below and the full Prescribing Information, including BOXED WARNING, and patient Medication Guide found on www.COPIKTRA.com
COPIKTRA has been added to the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL, FL and Marginal Zone Lymphoma (MZL). The NCCN Guidelines are the standard physician resource for determining the appropriate course of treatment for patients. COPIKTRA is not approved for use in MZL.
A PDF copy of this poster presentation is available here.
Verastem Oncology is committed to helping patients with CLL/SLL and FL access COPIKTRA through our Verastem Cares™ program. Verastem Cares is a comprehensive, personalized program designed to provide information and assistance to patients who have been prescribed COPIKTRA.
Patients, physicians, pharmacists, or other healthcare professionals with questions about COPIKTRA should contact 1-833-570-2273 (CARE) or visit www.COPIKTRA.com.
About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are cancers that affect lymphocytes and are essentially the same disease, with the only difference being the location where the cancer primarily occurs. When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL. The symptoms of CLL/SLL include a tender, swollen abdomen and feeling full even after eating only a small amount. Other symptoms can include fatigue, shortness of breath, anemia, bruising easily, night sweats, weight loss, and frequent infections. However, many patients with CLL/SLL will live for years without symptoms. There are approximately 200,000 patients in the US affected by CLL/SLL with nearly 20,000 new diagnoses this year alone. While there are therapies currently available, real-world data reveals that a significant number of patients either relapse following treatment, become refractory to current agents, or are unable to tolerate treatment, representing a significant medical need. 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 CLL/SLL.
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.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a commercial biopharmaceutical company committed to the development and commercialization of medicines to improve the lives of patients diagnosed with cancer. We are driven by the strength, tenacity and courage of those battling cancer – single-minded in our resolve to deliver new therapies that not only keep cancer at bay, but improve the lives of patients diagnosed with cancer. Because for us, it’s personal.
Our first FDA approved product is now available for the treatment of patients with certain types of indolent non-Hodgkin’s lymphoma (iNHL). Our pipeline comprises product candidates that seek to treat cancer by modulating the local tumor microenvironment. For more information, please visit www.verastem.com.
SOURCE: Veraste Oncology
Post Views: 36
Data Presented at the 23rd Annual International Congress on Hematologic Malignancies
COPIKTRA Demonstrates Progression-Free Survival of 16.4 Months and an Overall Response Rate of 78% in Adult Patients with CLL/SLL After At Least Two Prior Therapies
BOSTON, MA, USA I March 04, 2019 I 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, today announced a poster highlighting clinical data from the Phase 3 DUO study evaluating COPIKTRA (duvelisib) in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies was presented at the 23rd Annual International Congress on Hematologic Malignancies (ICHM), which took place February 28 – March 3, 2019, in Miami, FL. COPIKTRA, an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, received approval from the U.S. Food and Drug Administration (FDA) for this same indication in September 2018.
COPIKTRA also received accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. The accelerated approval was based on overall response rate and continued approval for this indication may be contingent upon confirmatory trials.
“Although the treatment landscape in CLL/SLL has advanced in recent years, there remains an unmet need with many patients progressing or relapsing,” commented Ian Flinn, MD, PhD, Director, Lymphoma/CLL Program at Sarah Cannon Research Institute and lead investigator of the DUO study. “These data from the randomized Phase 3 DUO study, which were calculated from patients who had previously received at least two prior therapies, demonstrate that COPIKTRA achieved a 78% overall response rate and progression-free survival of 16.4 months, compared to 9.1 months for ofatumumab, in patients with relapsed or refractory CLL/SLL, including in high risk patients with the 17p deletion. With convenient oral administration COPIKTRA has been a valuable addition to the treatment landscape for CLL/SLL patients and for the physicians who treat them.”
Results of the Phase 3 DUO Study Evaluating COPIKTRA in Adult Patients with Relapsed or Refractory CLL/SLL After At Least Two Prior Therapies
The randomized, multicenter, open-label, Phase 3 DUO study, compared COPIKTRA versus ofatumumab in 319 adult patients with CLL (n=312) or SLL (n=7) after at least one prior therapy. The study randomized patients with a 1:1 ratio to receive either COPIKTRA 25mg twice daily until disease progression or unacceptable toxicity, or ofatumumab, an approved standard of care treatment for use in CLL/SLL, for 7 cycles.
The approval of COPIKTRA was based on efficacy and safety analysis of patients with at least 2 prior lines of therapy, where the benefit:risk appeared greater in this more heavily pretreated population compared to the overall trial population.
In this subset (95 randomized to COPIKTRA, 101 to ofatumumab), the median patient age was 69 years (range: 40 to 90 years), 59% were male, and 88% had an ECOG performance status of 0 or 1. Forty-six percent received 2 prior lines of therapy, and 54% received 3 or more prior lines. At baseline, 52% of patients had at least one tumor ≥ 5 cm, and 22% of patients had a documented 17p deletion.
During randomized treatment, the median duration of exposure to COPIKTRA was 13 months (range: 0.2 to 37), with 80% of patients receiving at least 6 months and 52% receiving at least 12 months of COPIKTRA. The median duration of exposure to ofatumumab was 5 months (range: < 0.1 to 6).
Efficacy was based on progression-free survival (PFS) as assessed by an Independent Review Committee (IRC). Other efficacy measures included overall response rate (ORR). Efficacy of COPIKTRA compared to ofatumumab specifically in patients treated with at least two prior therapies is below.
| |
|
|
|
|
|
|
|
|
|
|
|
| Outcome per IRC |
|
|
|
COPIKTRA
N = 95
|
|
|
|
Ofatumumab
N = 101
|
|
|
|
| PFS |
|
|
|
| Number of events, n (%) |
|
|
|
55 (58) |
|
|
|
70 (69) |
|
|
|
| Progressive disease |
|
|
|
44 |
|
|
|
62 |
|
|
|
| Death |
|
|
|
11 |
|
|
|
8 |
|
|
|
| Median PFS (SE), months a |
|
|
|
16.4 (2.1) |
|
|
|
9.1 (0.5) |
|
|
|
|
Hazard Ratio (SE), b
COPIKTRA/ofatumumab
|
|
|
|
0.40 (0.2) |
|
|
|
| Response rate |
|
|
|
| ORR, n (%) c |
|
|
|
74 (78) |
|
|
|
39 (39) |
|
|
|
| CR |
|
|
|
0 (0) |
|
|
|
0 (0) |
|
|
|
| PR |
|
|
|
74 (78) |
|
|
|
39 (39) |
|
|
|
| Difference in ORR, % (SE) |
|
|
|
39 (6.4) |
|
|
|
| |
|
|
|
|
|
|
|
Abbreviations: CR = complete response; IRC = Independent Review Committee; PFS = progression-free survival; PR = partial response; SE = standard error
a Kaplan-Meier estimate
b Standard Error of ln(hazard ratio) = 0.2
c IWCLL or revised IWG response criteria, with modification for treatment-related lymphocytosis
COPIKTRA has a BOXED WARNING for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem Oncology has implemented a Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on COPIKTRA.
Additionally, COPIKTRA is also associated with adverse reactions which may require dose reduction, treatment delay or discontinuation of COPIKTRA. WARNINGS AND PRECAUTIONS are provided for infections, diarrhea or colitis, cutaneous reactions, pneumonitis, 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 the Important Safety Information below and the full Prescribing Information, including BOXED WARNING, and patient Medication Guide found on www.COPIKTRA.com
COPIKTRA has been added to the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL, FL and Marginal Zone Lymphoma (MZL). The NCCN Guidelines are the standard physician resource for determining the appropriate course of treatment for patients. COPIKTRA is not approved for use in MZL.
A PDF copy of this poster presentation is available here.
Verastem Oncology is committed to helping patients with CLL/SLL and FL access COPIKTRA through our Verastem Cares™ program. Verastem Cares is a comprehensive, personalized program designed to provide information and assistance to patients who have been prescribed COPIKTRA.
Patients, physicians, pharmacists, or other healthcare professionals with questions about COPIKTRA should contact 1-833-570-2273 (CARE) or visit www.COPIKTRA.com.
About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are cancers that affect lymphocytes and are essentially the same disease, with the only difference being the location where the cancer primarily occurs. When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL. The symptoms of CLL/SLL include a tender, swollen abdomen and feeling full even after eating only a small amount. Other symptoms can include fatigue, shortness of breath, anemia, bruising easily, night sweats, weight loss, and frequent infections. However, many patients with CLL/SLL will live for years without symptoms. There are approximately 200,000 patients in the US affected by CLL/SLL with nearly 20,000 new diagnoses this year alone. While there are therapies currently available, real-world data reveals that a significant number of patients either relapse following treatment, become refractory to current agents, or are unable to tolerate treatment, representing a significant medical need. 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 CLL/SLL.
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.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a commercial biopharmaceutical company committed to the development and commercialization of medicines to improve the lives of patients diagnosed with cancer. We are driven by the strength, tenacity and courage of those battling cancer – single-minded in our resolve to deliver new therapies that not only keep cancer at bay, but improve the lives of patients diagnosed with cancer. Because for us, it’s personal.
Our first FDA approved product is now available for the treatment of patients with certain types of indolent non-Hodgkin’s lymphoma (iNHL). Our pipeline comprises product candidates that seek to treat cancer by modulating the local tumor microenvironment. For more information, please visit www.verastem.com.
SOURCE: Veraste Oncology
Post Views: 36
