Secura Bio Announces Enrollment Completion of the COPIKTRA® (duvelisib) Study (PRIMO) in Peripheral T-cell Lymphoma

SUMMERLIN, Nev., April 8, 2021 /PRNewswire/ -- Secura Bio, Inc. (Secura Bio) - (www.securabio.com), an integrated pharmaceutical company dedicated to the worldwide development and commercialization of impactful oncology therapies, today announced that it has completed enrollment, with 101 patients, into the PRIMO study, which is evaluating COPIKTRA for the treatment of patients with relapsed or refractory Peripheral T-cell Lymphoma (PTCL). The completion of study enrollment is an important milestone in the continued development of COPIKTRA to treat T-cell lymphomas, a disease category for which it is not currently indicated.

The PRIMO study is a global, multi-center, open-label, parallel cohort registration-directed Phase 2 study. In the dose optimization portion of the study, patients were randomized to receive COPIKTRA  25mg twice daily (cohort 1) or COPIKTRA  75mg twice daily continuously (cohort 2) until disease progression or unacceptable toxicity. Based on the dose optimization results, an expansion group was added in which COPIKTRA was dosed at 75mg twice daily for two cycles, followed by 25mg twice daily, until disease progression or unacceptable toxicity. The primary endpoint in the expansion phase of the study is independent review committee assessed overall response rate (ORR). Secondary endpoints include duration of response (DOR) and safety.

COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and gamma pathways, which are involved in the proliferation and sustenance of malignant cells.

"Secura Bio will continue to aggressively support the development of COPIKTRA in the treatment of T-cell malignancies, because these patients often have limited therapeutic options and generally poor outcomes, and because PI3K inhibition appears to be a relevant, safe and promising mechanism of action" said Dr. David Cohan, Chief Medical Officer of Secura Bio.

For the treatment of PTCL, COPIKTRA monotherapy has received Fast Track status and Orphan Drug Designation, and investigations are imminently planned in combination with other proven anti-cancer agents.

"Secura Bio now has two meaningful oncology drugs with novel modes of action that offer the potential to build a broad portfolio of indications in hematologic and solid malignancies. We will also fully explore the combination of COPIKTRA with FARYDAK® (panobinostat), Secura Bio's pan-HDAC inhibitor" said Joseph M. Limber, President and CEO of Secura Bio.

Interim results of the PRIMO study are expected to be published later in 2021.

About Secura Bio, Inc.

Secura Bio is an integrated, commercial-stage pharmaceutical company dedicated to the worldwide commercialization of significant oncology therapies for physicians and their patients.  For more information on Secura Bio, please visit www.securabio.com.

About COPIKTRA (duvelisib)

COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first US approved dual inhibitor of PI3K-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant cells. PI3K signaling may lead to the proliferation of malignant cells and is thought to play a role in the formation and maintenance of a supportive tumor microenvironment.  COPIKTRA is indicated in the United States 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 has accelerated approval for refractory follicular lymphoma (FL) after at least two prior systemic therapies. COPIKTRA is also being developed for the treatment of peripheral T-cell lymphoma (PTCL), for which it has received Fast Track status in the United States and is being investigated in combination with other agents through investigator-sponsored studies.  For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

IMPORTANT SAFETY INFORMATION ABOUT COPIKTRA

WARNING: FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and PNEUMONITIS

See full prescribing information for complete boxed warning

• Fatal and/or serious infections occurred in 31% (4% fatal) of COPIKTRA-treated patients. Monitor for signs and symptoms of infection. Withhold COPIKTRA if infection is suspected.
• Fatal and/or serious diarrhea or colitis occurred in 18% (<1% fatal) of COPIKTRA-treated patients. Monitor for the development of severe diarrhea or colitis. Withhold COPIKTRA.
• Fatal and/or serious cutaneous reactions occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Withhold COPIKTRA.
• Fatal and/or serious pneumonitis occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Monitor for pulmonary symptoms and interstitial infiltrates. Withhold COPIKTRA.

INDICATIONS AND USAGE

COPIKTRA is a kinase inhibitor indicated for the treatment of adult patients with:

• Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies.
• Relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. Accelerated approval based on overall response rate; continued approval may be contingent upon confirmatory trials.

WARNINGS AND PRECAUTIONS

• Hepatotoxicity: Monitor hepatic function.
• Neutropenia: Monitor blood counts.
• Embryo-Fetal toxicity: COPIKTRA can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) are diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

DRUG INTERACTIONS

• CYP3A inducers: Avoid co-administration with strong CYP3A inducers.
• CYP3A inhibitors: Monitor for COPIKTRA toxicities when co-administered with strong or moderate CYP3A inhibitors. Reduce COPIKTRA dose to 15 mg twice daily when co-administered with strong CYP3A4 inhibitors.
• CYP3A substrates: Monitor for signs of toxicities when co-administering COPIKTRA with sensitive CYP3A substrates.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed.

Please click here to see full Prescribing Information, including Boxed WARNING, for COPIKTRA (duvelisib).

About Peripheral T-cell Lymphoma

Peripheral T-cell lymphoma (PTCL) is a rare, aggressive type of non-Hodgkin lymphoma (NHL) that develops in mature white blood cells called "T cells" and "natural killer (NK) cells"¹ which circulate with the lymphatic system. PTCL accounts for between 10-15% of all non-Hodgkin lymphomas (NHLs) and generally affects people aged 60 years and older. Although there are many different subtypes of peripheral T-cell lymphoma, they often present in a similar way, with widespread, enlarged, painless lymph nodes in the neck, armpit or groin. There are currently no well-established standards of care for patients with relapsed or refractory disease.

About FARYDAK^® (panobinostat)

INDICATION

FARYDAK (panobinostat) capsules, a histone deacetylase inhibitor, in combination with bortezomib and dexamethasone, is indicated for the treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION ABOUT FARYDAK

WARNING: FATAL AND SERIOUS TOXICITIES: SEVERE DIARRHEA AND CARDIAC TOXICITIES

Severe diarrhea occurred in 25% of FARYDAK treated patients. Monitor for symptoms, institute anti-diarrheal treatment, interrupt FARYDAK and then reduce dose or discontinue FARYDAK.

Severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes have occurred in patients receiving FARYDAK. Arrhythmias may be exacerbated by electrolyte abnormalities. Obtain ECG and electrolytes at baseline and periodically during treatment as clinically indicated.

Diarrhea

• Severe diarrhea occurred in 25% of patients treated with FARYDAK. Diarrhea of any grade occurred in 68% of patients treated with FARYDAK compared with 42% of patients in the control arm. Diarrhea can occur at any time. Ensure patients have antidiarrheal medications on hand, and initiate antidiarrheal medication at the onset of diarrhea
• Monitor hydration status and electrolyte blood levels at baseline, and weekly (or more often as clinically indicated) during therapy, and correct to prevent dehydration and electrolyte disturbances
• Interrupt FARYDAK at the onset of moderate diarrhea (4-6 stools/day
• For life-threatening diarrhea (grade 4), permanently discontinue FARYDAK and bortezomib
• For severe diarrhea (≥7 stools/day), or IV fluids or hospitalization required (grade 3), interrupt FARYDAK and bortezomib until resolved and restart both at reduced doses
• For moderate diarrhea (4-6 stools/day, grade 2), interrupt FARYDAK until resolved and restart at same dose. Consider interruption of bortezomib until resolved and restart at same dose

Cardiac Toxicities

• Arrhythmias occurred in 12% of patients treated with FARYDAK compared with 5% of patients in the control arm. Cardiac ischemic events occurred in 4% of patients treated with FARYDAK compared with 1% of patients in the control arm
• Do not initiate FARYDAK treatment in patients with history of recent myocardial infarction or unstable angina
• ECG abnormalities such as ST-segment depression and T-wave abnormalities occurred more frequently in patients receiving FARYDAK compared with the control arm: 22% vs 4% and 40% vs 18%, respectively
• FARYDAK may prolong QT interval. Do not initiate treatment with FARYDAK in patients with a QTcF >450 msec or clinically significant baseline ST-segment or T-wave abnormalities
• Arrhythmias may be exacerbated by electrolyte abnormalities. If during treatment with FARYDAK, the QTcF increases to ≥480 msec, interrupt treatment. Correct any electrolyte abnormalities. If QT prolongation does not resolve, permanently discontinue treatment. Obtain ECG at baseline and periodically during treatment. Monitor electrolytes during treatment with FARYDAK, and correct abnormalities as clinically indicated

Hemorrhage

• Fatal and serious cases of gastrointestinal and pulmonary hemorrhage occurred
• In the phase 3 registration trial, 5 patients receiving FARYDAK, compared with 1 patient in the control arm, died due to a hemorrhagic event. All 5 patients had grade ≥3 thrombocytopenia at the time of the event
• Grade 3/4 hemorrhage was reported in 4% of patients treated with FARYDAK and 2% of patients in the control arm
• Monitor platelet counts and transfuse as needed

Myelosuppression

• FARYDAK causes myelosuppression including severe thrombocytopenia, neutropenia, and anemia. Obtain a baseline CBC, and monitor the CBC weekly during treatment (or more often if clinically indicated or in patients >65 years of age)
• Thrombocytopenia
• In the phase 3 registration trial, 67% of patients treated with FARYDAK developed Grade 3/4 thrombocytopenia compared with 31% in the control arm
• Thrombocytopenia led to treatment interruption and/or dose modification in 31% of patients receiving FARYDAK
• For patients receiving FARYDAK, 33% required platelet transfusion
• For patients with platelet count <50 x 10⁹/L with bleeding (grade 3) or <25 x 10⁹/L (grade 4)
• Interrupt FARYDAK therapy and monitor platelets at least weekly until ≥50 x 10⁹/L, and restart at reduced dose
• Interrupt bortezomib until thrombocytopenia resolves ≥50 x 10⁹/L
• If only 1 dose of bortezomib was omitted prior to correction to these levels, restart bortezomib at same dose
• If ≥2 doses were omitted consecutively, or within the same cycle, restart at a reduced dose
• For patients with platelet count <50 x 10⁹/L (grade 3), maintain FARYDAK and bortezomib doses and monitor platelet counts at least weekly
• For patients with severe thrombocytopenia, consider platelet transfusions
• Discontinue FARYDAK if thrombocytopenia does not improve despite the recommended treatment modifications or if repeated platelet transfusions are required
• Neutropenia
• Severe neutropenia occurred in 34% of patients treated with FARYDAK compared with 11% of patients in the control arm
• Neutropenia led to treatment interruption and/or dose modification in 10% of patients receiving FARYDAK
• Use of granulocyte-colony stimulating factor (G-CSF) was 13% in patients treated with FARYDAK
• For patients with ANC <0.5 x 10⁹/L (grade 4)
• Interrupt FARYDAK and bortezomib therapy until ANC is ≥1.0 x 10⁹/L. Restart FARYDAK at reduced dose
• If only 1 dose of bortezomib was omitted prior to correction to these levels, restart at same dose. If ≥2 doses of bortezomib were omitted consecutively, or within the same cycle, restart at reduced dose
• For patients with ANC <1.0 x 10⁹/L (grade 3) and febrile neutropenia (any grade)
• Interrupt FARYDAK and bortezomib therapy until febrile neutropenia is resolved and ANC >1.0 x 10⁹/L
• Restart FARYDAK at reduced dose
• If only 1 dose of bortezomib was omitted prior to correction to these levels, restart at same dose. If ≥2 doses of bortezomib were omitted consecutively, or within the same cycle, restart at reduced dose
• For patients with ≥2 occurrences of ANC between 0.5 – 0.75 x 10⁹/L (grade 3)
• Interrupt FARYDAK therapy until ANC ≥1.0 x 10⁹/L, and restart at same dose
• Maintain bortezomib dose
• For patients with ANC between 0.75 – 1.0 x 10⁹/L (grade 3)
• Maintain FARYDAK and bortezomib doses
• For grade 3 or 4 neutropenia, consider dose reduction and/or the use of growth factors
• Discontinue FARYDAK if neutropenia does not improve despite dose modifications, CSF, or in case of severe infection
• Anemia
• For patients with hemoglobin <8 g/dL (grade 3), interrupt FARYDAK until hemoglobin ≥10 g/dL. Restart at reduced dose

Infections

• Severe infections occurred in 31% of patients (including 10 deaths) treated with FARYDAK compared with 24% of patients (including 6 deaths) in the control arm
• FARYDAK treatment should not be initiated in patients with active infections
• Monitor patients for signs and symptoms of infections during treatment; if a diagnosis of infection is made, institute appropriate anti-infective treatment promptly and consider interruption or discontinuation of FARYDAK

Hepatotoxicity

• Hepatic dysfunction, primarily elevations in aminotransferases and total bilirubin, occurred in patients treated with FARYDAK
• Monitor liver function prior to and regularly during treatment. If abnormal liver function tests are observed, consider dose adjustments. Follow patient until values return to normal or pretreatment levels
• Avoid use in patients with severe hepatic impairment
• Reduce the starting dose of FARYDAK to 15 mg or 10 mg in patients with mild or moderate hepatic impairment, respectively

Embryo-Fetal Toxicity

• FARYDAK can cause fetal harm when administered to a pregnant woman
• If FARYDAK is used during pregnancy, or if the patient becomes pregnant while taking FARYDAK, the patient should be apprised of the potential hazard to the fetus
• Advise females of reproductive potential to avoid becoming pregnant while taking FARYDAK
• Advise sexually active females of reproductive potential to use effective contraception while taking FARYDAK, and for at least 3 months after the last dose of FARYDAK
• Advise sexually active men to use condoms while on treatment, and for at least 6 months after their last dose of FARYDAK

DRUG INTERACTIONS

• Reduce dose to 10 mg when coadministered with strong CYP3A inhibitors. Instruct patients to avoid star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice
• Avoid the concomitant use of strong CYP3A inducers
• Avoid coadministration with sensitive CYP2D6 substrates or CYP2D6 substrates that have a narrow therapeutic index. If concomitant use of CYP2D6 substrates is unavoidable, monitor patients frequently for adverse reactions
• Concomitant use of antiarrhythmic medicines, and other drugs that are known to prolong the QT interval, is not recommended. Antiemetic drugs with known QT-prolonging risk can be used with frequent ECG monitoring

ADVERSE REACTIONS

• The most common adverse reactions (incidence of at least 20%) in clinical studies are diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, and vomiting
• The most common nonhematologic laboratory abnormalities (incidence ≥40%) are hypocalcemia, hypophosphatemia, hypoalbuminemia, hypokalemia, hyponatremia, and increased creatinine. The most common hematologic laboratory abnormalities (incidence ≥60%) are thrombocytopenia, lymphopenia, leukopenia, neutropenia, and anemia
• Serious adverse events (SAEs) occurred in 60% of patients in the FARYDAK arm. The most frequent (≥5%) treatment-emergent SAEs reported for patients treated with FARYDAK were pneumonia, diarrhea, thrombocytopenia, fatigue, and sepsis

Please click here to see full Prescribing Information, including Boxed WARNING, for FARYDAK (panobinostat) capsules.

To report Adverse Reactions, contact FDA at 1-800-FDA-1088 (1-800-332-1088) or www.fda.gov/medwatch and Secura Bio at 1-800-9SECURA (1-844-973-2872).

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