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FDA Approvals in CML, CTCL, CMV Infection, and Tumor Assay, and Clinical Holds Lifted

Gina Columbus
Published: Monday, Nov 20, 2017



Today-

FDA approvals in chronic myeloid leukemia, cutaneous T-cell lymphoma, cytomegalovirus infection, and a tumor assay, and clinical holds lifted from CAR T-cell therapy trials.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved dasatinib for the treatment of pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.

The approval is based on results in 97 pediatric patients with CP-CML enrolled across 2 studies with dasatinib. One was an open-label, nonrandomized, single-arm phase II trial and the other was an open-label, nonrandomized, dose-ranging phase I trial. In the single-arm trial, 51 patients were newly diagnosed, and the remaining 46, 29 from the single-arm study and 17 from the dose-ranging trial, were intolerant or resistant to prior imatinib.

At a median follow-up of 4.5 years, more than half of the responding patients in the treatment-naïve cohort had not progressed at the time of the data cutoff. Also, the median duration of complete cytogenetic response, major cytogenetic response, and major molecular response could not be estimated. The same was true at the median follow-up time of 5.2 years for the previously treated cohort.

The range of duration of response for the newly diagnosed patients was 2.5 to 66.5 months for CCyR, 1.4 to 66.5 months for MCyR, 5.4 to 72.5 months for patients who achieved MMR by month 24, and 0.03 to 72.5 months for patients who achieved MMR at any time. Among the imatinib-intolerant cohort, the DOR ranges were 2.4 to 86.9 months for CCyR, 2.4 to 86.9 months for MCyR, and 2.6 to 73.6 months for MMR.

*****************************************

In cutaneous T-cell lymphoma, the FDA approved brentuximab vedotin as a treatment for patients with cutaneous T-cell lymphoma who have received prior systemic therapy.

The approval for the antibody-drug conjugate is specifically for patients with primary cutaneous anaplastic large cell lymphoma and CD30-expressing mycosis fungoides. MF and pcALCL are the most common subtypes of CTCL.

The FDA considered data from the international, open-label, phase III ALCANZA trial, in which brentuximab vedotin induced responses lasting at least 4 months in 56.3% of patients versus 12.5% in patients receiving physician’s choice of standard therapies.

Results showed that, at a median follow-up of 22.9 months, the median progression-free survival was 16.7 months with brentuximab vedotin versus 3.5 months with physician’s choice. The objective response rate was 67% versus 20%, with complete response rates of 16% versus 2%, in the brentuximab vedotin and control arms, respectively. Symptom reduction, as measured by Skindex-29, was significantly better with brentuximab vedotin versus physician’s choice.

*****************************************

The FDA has approved letermovir as a treatment to prevent cytomegalovirus infection in adult CMV-seropositive patients treated with an allogeneic hematopoietic stem cell transplant.

Letermovir is a non-nucleoside CMV inhibitor that targets the viral terminase complex to prevent replication.

The decision was based on a significant reduction in CMV infection rates in a phase III study, results of which showed that 37.5% of patients treated with letermovir developed CMV by week 24 post-transplant compared with 60.6% of those in the placebo arm.

Moreover, letermovir was associated with lower all-cause mortality versus placebo at 24 weeks. The median time to engraftment and bone marrow suppression rates were similar in each group.

Merck plans to make the medication available in December 2017 at a list price of $195.00 for a tablet version and $270.00 for an injection formulation.

******************************

The IMPACT tumor profiling assay has been approved by the FDA. The assay, which stands for Integrated Mutation Profiling of Actionable Cancer Targets, is a tumor profiling test developed at Memorial Sloan Kettering Cancer Center. This is an in vitro diagnostic test that can identify more tumor biomarkers than any test previously reviewed by the agency.

IMPACT uses next-generation sequencing to rapidly identify the presence of mutations in 468 unique genes, as well as other molecular changes in a tumor’s genomic makeup.

The test compares a patient’s tumor tissue with a sample of normal tissue to detect genetic alterations. While it is intended to provide information on cancer biomarkers and help guide treatment options, the FDA cautions its results should not be taken as definitive when making treatment decisions.

The FDA determined that IMPACT is more than 99% accurate and capable of detecting a mutation at a frequency of approximately 5%. Compared with traditional methods of detection, detection of microsatellite instability was concordant more than 92% of the time across multiple cancer types in 175 cases.

**************************************

Clinical holds on 2 phase I trials exploring a gene-edited allogeneic CAR T-cell therapy known as UCART123 have been lifted by the FDA.

Cellectis, the developer of UCART123 is working with investigators and clinical sites to obtain approval from its institutional review board on the revised protocols requested by the FDA and resume patient enrollment.

The agency halted UCART trials in September 2017 following the death of an elderly patient being treated for blastic plasmacytoid dendritic cell neoplasm. The FDA also cited the case of a 58-year-old patient who developed grade 3 cytokine release syndrome and grade 4 capillary leak syndrome while undergoing treatment for acute myeloid leukemia. Both conditions eventually resolved after she was treated in an intensive care unit.

Cellectis is developing UCART123 as a treatment for BPDCN and AML. It was designated an Investigational New Drug in February 2017, making it the first allogenic gene-edited CAR T-cell agent approved for clinical trial.

UCART’s process differs from the CAR T-cell therapy tisagenlecleucel in that it is allogeneic and could treat any patient using T cells harvested from potentially any donor.

Cellectis says its “off-the-shelf” allogenic process is faster, easier to develop, and significantly less expensive than autologous CAR T-cell therapy. The price for a one-time treatment with tisagenlecleucel is set at $475,000.

**************************************

This week, we sat down with Dr Elizabeth Mittendorf of The University of Texas MD Anderson Cancer to discuss neoadjuvant approaches in HER2-positive breast cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
 
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Today-

FDA approvals in chronic myeloid leukemia, cutaneous T-cell lymphoma, cytomegalovirus infection, and a tumor assay, and clinical holds lifted from CAR T-cell therapy trials.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved dasatinib for the treatment of pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.

The approval is based on results in 97 pediatric patients with CP-CML enrolled across 2 studies with dasatinib. One was an open-label, nonrandomized, single-arm phase II trial and the other was an open-label, nonrandomized, dose-ranging phase I trial. In the single-arm trial, 51 patients were newly diagnosed, and the remaining 46, 29 from the single-arm study and 17 from the dose-ranging trial, were intolerant or resistant to prior imatinib.

At a median follow-up of 4.5 years, more than half of the responding patients in the treatment-naïve cohort had not progressed at the time of the data cutoff. Also, the median duration of complete cytogenetic response, major cytogenetic response, and major molecular response could not be estimated. The same was true at the median follow-up time of 5.2 years for the previously treated cohort.

The range of duration of response for the newly diagnosed patients was 2.5 to 66.5 months for CCyR, 1.4 to 66.5 months for MCyR, 5.4 to 72.5 months for patients who achieved MMR by month 24, and 0.03 to 72.5 months for patients who achieved MMR at any time. Among the imatinib-intolerant cohort, the DOR ranges were 2.4 to 86.9 months for CCyR, 2.4 to 86.9 months for MCyR, and 2.6 to 73.6 months for MMR.

*****************************************

In cutaneous T-cell lymphoma, the FDA approved brentuximab vedotin as a treatment for patients with cutaneous T-cell lymphoma who have received prior systemic therapy.

The approval for the antibody-drug conjugate is specifically for patients with primary cutaneous anaplastic large cell lymphoma and CD30-expressing mycosis fungoides. MF and pcALCL are the most common subtypes of CTCL.

The FDA considered data from the international, open-label, phase III ALCANZA trial, in which brentuximab vedotin induced responses lasting at least 4 months in 56.3% of patients versus 12.5% in patients receiving physician’s choice of standard therapies.

Results showed that, at a median follow-up of 22.9 months, the median progression-free survival was 16.7 months with brentuximab vedotin versus 3.5 months with physician’s choice. The objective response rate was 67% versus 20%, with complete response rates of 16% versus 2%, in the brentuximab vedotin and control arms, respectively. Symptom reduction, as measured by Skindex-29, was significantly better with brentuximab vedotin versus physician’s choice.

*****************************************

The FDA has approved letermovir as a treatment to prevent cytomegalovirus infection in adult CMV-seropositive patients treated with an allogeneic hematopoietic stem cell transplant.

Letermovir is a non-nucleoside CMV inhibitor that targets the viral terminase complex to prevent replication.

The decision was based on a significant reduction in CMV infection rates in a phase III study, results of which showed that 37.5% of patients treated with letermovir developed CMV by week 24 post-transplant compared with 60.6% of those in the placebo arm.

Moreover, letermovir was associated with lower all-cause mortality versus placebo at 24 weeks. The median time to engraftment and bone marrow suppression rates were similar in each group.

Merck plans to make the medication available in December 2017 at a list price of $195.00 for a tablet version and $270.00 for an injection formulation.

******************************

The IMPACT tumor profiling assay has been approved by the FDA. The assay, which stands for Integrated Mutation Profiling of Actionable Cancer Targets, is a tumor profiling test developed at Memorial Sloan Kettering Cancer Center. This is an in vitro diagnostic test that can identify more tumor biomarkers than any test previously reviewed by the agency.

IMPACT uses next-generation sequencing to rapidly identify the presence of mutations in 468 unique genes, as well as other molecular changes in a tumor’s genomic makeup.

The test compares a patient’s tumor tissue with a sample of normal tissue to detect genetic alterations. While it is intended to provide information on cancer biomarkers and help guide treatment options, the FDA cautions its results should not be taken as definitive when making treatment decisions.

The FDA determined that IMPACT is more than 99% accurate and capable of detecting a mutation at a frequency of approximately 5%. Compared with traditional methods of detection, detection of microsatellite instability was concordant more than 92% of the time across multiple cancer types in 175 cases.

**************************************

Clinical holds on 2 phase I trials exploring a gene-edited allogeneic CAR T-cell therapy known as UCART123 have been lifted by the FDA.

Cellectis, the developer of UCART123 is working with investigators and clinical sites to obtain approval from its institutional review board on the revised protocols requested by the FDA and resume patient enrollment.

The agency halted UCART trials in September 2017 following the death of an elderly patient being treated for blastic plasmacytoid dendritic cell neoplasm. The FDA also cited the case of a 58-year-old patient who developed grade 3 cytokine release syndrome and grade 4 capillary leak syndrome while undergoing treatment for acute myeloid leukemia. Both conditions eventually resolved after she was treated in an intensive care unit.

Cellectis is developing UCART123 as a treatment for BPDCN and AML. It was designated an Investigational New Drug in February 2017, making it the first allogenic gene-edited CAR T-cell agent approved for clinical trial.

UCART’s process differs from the CAR T-cell therapy tisagenlecleucel in that it is allogeneic and could treat any patient using T cells harvested from potentially any donor.

Cellectis says its “off-the-shelf” allogenic process is faster, easier to develop, and significantly less expensive than autologous CAR T-cell therapy. The price for a one-time treatment with tisagenlecleucel is set at $475,000.

**************************************

This week, we sat down with Dr Elizabeth Mittendorf of The University of Texas MD Anderson Cancer to discuss neoadjuvant approaches in HER2-positive breast cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
 
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