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Breakthrough Designation in AML, Application Submitted in Myeloma, Promising Data in SCLC, and More

Gina Columbus
Published: Monday, Apr 01, 2019



Today-

A breakthrough therapy designation in acute myeloid leukemia, an application submitted in multiple myeloma, promising findings in small cell lung cancer and myeloma, a trial discontinued in ovarian cancer, and policy changes to improve mammography services.

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

The FDA has granted a breakthrough therapy designation to the combination of ivosidenib and azacitidine for the treatment of newly diagnosed patients with IDH1-mutant acute myeloid leukemia who are older than 75 years old or are ineligible for intensive induction chemotherapy.

The decision is based on data from a phase I/II trial, in which the combination of ivosidenib plus azacitidine led to a 78% overall response rate, including a 57% complete response rate in this patient population. The median duration of CR had not been reached, and the 1-year overall survival rate was 82%.

Additionally, the mean neutrophil and platelet counts were maintained near or above thresholds for CR with partial hematologic recovery while on study treatment with ivosidenib and azacitidine. As of the data cutoff, 14 patients remained on study.

Moreover, at a median 9.5-month follow-up, results showed that 65% of patients had a CR plus CRh, and the median time to response was 1.8 months. The median time to CR was 3.5 months.

Single-agent ivosidenib is currently indicated for the treatment of adult patients with relapsed/refractory AML with IDH1 mutations.

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

In multiple myeloma, a supplemental biologics license application has been submitted to the FDA for daratumumab in combination with bortezomib, thalidomide, and dexamethasone for the treatment of newly diagnosed patients who are eligible for autologous stem cell transplant.

The application is based on findings from part 1 of the phase III CASSIOPEIA trial, in which the stringent complete response rate was 28.9% in patients who received the daratumumab regimen versus 20.3% in those who received VTd alone following induction and consolidation therapy.

Part 1 results also showed that the safety profile of daratumumab in combination with VTd is consistent with the known profiles of VTd as well as the known tolerability of daratumumab.

In the second part of CASSIOPEIA, which is ongoing, patients who achieved a partial response or better in part 1 of the trial will then be randomized to receive either maintenance daratumumab every 8 weeks for up to 2 years or observation.

Also based on these findings, a Type II variation application was recently submitted to the European Medicines Agency for the 4-drug regimen as a treatment for patients with newly diagnosed multiple myeloma who are eligible to undergo ASCT.

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

Lurbinectedin monotherapy achieved a high objective response rate in patients with relapsed small cell lung cancer, meeting the primary endpoint of a phase II trial by both investigator review and an independent review committee.

In the multicenter, single-arm, phase II basket study, investigators evaluated the safety and efficacy of lurbinectedin with SCLC, head and neck cancer, neuroendocrine tumors, biliary tract cancer, endometrial cancer, BRCA1/2-mutant metastatic breast cancer, carcinoma of unknown primary site, germ cell tumors, and Ewing’s family of tumors.

Preliminary phase II data of the SCLC cohort showed that the ORR was 39.3%, the clinical benefit rate was 50.8%, and the disease control rate was 73.8%. Additionally, the median duration of response was 6.2 months, the median progression-free survival was 4.1 months, and the median overall survival was 11.8 months.

Updated findings are slated to be presented at an upcoming medical meeting.

The FDA granted lurbinectedin an orphan drug designation in August 2018, which was followed by the European Medicines Agency decision to also grant the agent orphan drug designation in January 2019, both in SCLC.

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

In multiple myeloma, a final analysis of the DREAMM-1 study showed that the investigational antibody-drug conjugate GSK2857916 continued to improve progression-free survival in patients with relapsed/refractory disease.

Additionally, results showed that the ADC elicited an overall response rate of 60%; there were 3 complete responses and 2 stringent CRs. The median PFS was 12 months and the median duration of response was 14.3 months.

Among heavily pretreated patients who were refractory to both an immunomodulatory agent and a proteasome inhibitor, the median PFS was 7.9 months and the ORR was 56.3%. In patients who did not receive prior treatment with daratumumab, the ORR was 71.4% and the median PFS was 15.7 months. Patients who were double refractory and were previously treated with daratumumab had a median PFS of 6.2 months and an ORR of 38.5%. In those patients who did previously receive daratumumab, the median PFS was 6.8 months. No new safety signals were identified during the treatment period.

The FDA granted the antibody-drug conjugate a breakthrough therapy designation in November 2017 for the treatment of patients with relapsed/refractory multiple myeloma who have failed 3 or more prior lines of therapy. The agent also received PRIME designation from the European Medicines Agency.

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

The ongoing phase III JAVELIN Ovarian PARP 100 study, which was evaluating the efficacy and safety of avelumab in combination with chemotherapy followed by maintenance avelumab in combination with talazoparib in patients with locally advanced or metastatic ovarian cancer, has been discontinued.

The decision stems from factors that include previously announced interim data of the JAVELIN Ovarian 100 trial, which ended in December 2018 after an independent panel determined the study would not meet its primary endpoint of progression-free survival. Therefore, those data did not support continuation of JAVELIN Ovarian PARP 100 in an unselected patient population.

Although safety was not a deciding factor, additional reasons for terminating the trial included recently approved treatment options for patients with ovarian cancer, including the December 2018 FDA approval of olaparib as a maintenance treatment for patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to frontline platinum-based chemotherapy.

The companies, which emphasized a need to better understand the role of immunotherapy in ovarian cancer, have notified health authorities as well as study investigators of the decision to end the study. This discontinuation does not affect current indications of avelumab nor the rest of the ongoing JAVELIN clinical development program.

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

The FDA has proposed amendments to key policies to modernize breast cancer screening and improve mammography services to enable healthcare providers and patients to make more informed medical decisions.

The proposal would modify regulations that were issued under the Mammography Quality Standards Act, which had been passed by Congress and enforced by the FDA to help ensure the delivery of high-quality mammography services.

The proposed changes were drafted to improve patient understanding of the relationship between breast density and breast cancer risk, to provide physicians with more detailed information to improve mammogram assessments, and to provide the FDA with the ability to better enforce the MQSA regulations and actively address violations.

The planned amendments also call for the distribution of more detailed information regarding the mammogram facility to both patients and providers as a way to help the post-exam process run more smoothly.

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

This week, we sat down with Dr Richard Finn, of UCLA Geffen School of Medicine, and Dr Anthony El-Khoueiry, of USC Keck School of Medicine, who discussed the future treatment paradigm of hepatocellular carcinoma.

That’s all for today.

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

A breakthrough therapy designation in acute myeloid leukemia, an application submitted in multiple myeloma, promising findings in small cell lung cancer and myeloma, a trial discontinued in ovarian cancer, and policy changes to improve mammography services.

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

The FDA has granted a breakthrough therapy designation to the combination of ivosidenib and azacitidine for the treatment of newly diagnosed patients with IDH1-mutant acute myeloid leukemia who are older than 75 years old or are ineligible for intensive induction chemotherapy.

The decision is based on data from a phase I/II trial, in which the combination of ivosidenib plus azacitidine led to a 78% overall response rate, including a 57% complete response rate in this patient population. The median duration of CR had not been reached, and the 1-year overall survival rate was 82%.

Additionally, the mean neutrophil and platelet counts were maintained near or above thresholds for CR with partial hematologic recovery while on study treatment with ivosidenib and azacitidine. As of the data cutoff, 14 patients remained on study.

Moreover, at a median 9.5-month follow-up, results showed that 65% of patients had a CR plus CRh, and the median time to response was 1.8 months. The median time to CR was 3.5 months.

Single-agent ivosidenib is currently indicated for the treatment of adult patients with relapsed/refractory AML with IDH1 mutations.

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

In multiple myeloma, a supplemental biologics license application has been submitted to the FDA for daratumumab in combination with bortezomib, thalidomide, and dexamethasone for the treatment of newly diagnosed patients who are eligible for autologous stem cell transplant.

The application is based on findings from part 1 of the phase III CASSIOPEIA trial, in which the stringent complete response rate was 28.9% in patients who received the daratumumab regimen versus 20.3% in those who received VTd alone following induction and consolidation therapy.

Part 1 results also showed that the safety profile of daratumumab in combination with VTd is consistent with the known profiles of VTd as well as the known tolerability of daratumumab.

In the second part of CASSIOPEIA, which is ongoing, patients who achieved a partial response or better in part 1 of the trial will then be randomized to receive either maintenance daratumumab every 8 weeks for up to 2 years or observation.

Also based on these findings, a Type II variation application was recently submitted to the European Medicines Agency for the 4-drug regimen as a treatment for patients with newly diagnosed multiple myeloma who are eligible to undergo ASCT.

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

Lurbinectedin monotherapy achieved a high objective response rate in patients with relapsed small cell lung cancer, meeting the primary endpoint of a phase II trial by both investigator review and an independent review committee.

In the multicenter, single-arm, phase II basket study, investigators evaluated the safety and efficacy of lurbinectedin with SCLC, head and neck cancer, neuroendocrine tumors, biliary tract cancer, endometrial cancer, BRCA1/2-mutant metastatic breast cancer, carcinoma of unknown primary site, germ cell tumors, and Ewing’s family of tumors.

Preliminary phase II data of the SCLC cohort showed that the ORR was 39.3%, the clinical benefit rate was 50.8%, and the disease control rate was 73.8%. Additionally, the median duration of response was 6.2 months, the median progression-free survival was 4.1 months, and the median overall survival was 11.8 months.

Updated findings are slated to be presented at an upcoming medical meeting.

The FDA granted lurbinectedin an orphan drug designation in August 2018, which was followed by the European Medicines Agency decision to also grant the agent orphan drug designation in January 2019, both in SCLC.

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

In multiple myeloma, a final analysis of the DREAMM-1 study showed that the investigational antibody-drug conjugate GSK2857916 continued to improve progression-free survival in patients with relapsed/refractory disease.

Additionally, results showed that the ADC elicited an overall response rate of 60%; there were 3 complete responses and 2 stringent CRs. The median PFS was 12 months and the median duration of response was 14.3 months.

Among heavily pretreated patients who were refractory to both an immunomodulatory agent and a proteasome inhibitor, the median PFS was 7.9 months and the ORR was 56.3%. In patients who did not receive prior treatment with daratumumab, the ORR was 71.4% and the median PFS was 15.7 months. Patients who were double refractory and were previously treated with daratumumab had a median PFS of 6.2 months and an ORR of 38.5%. In those patients who did previously receive daratumumab, the median PFS was 6.8 months. No new safety signals were identified during the treatment period.

The FDA granted the antibody-drug conjugate a breakthrough therapy designation in November 2017 for the treatment of patients with relapsed/refractory multiple myeloma who have failed 3 or more prior lines of therapy. The agent also received PRIME designation from the European Medicines Agency.

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

The ongoing phase III JAVELIN Ovarian PARP 100 study, which was evaluating the efficacy and safety of avelumab in combination with chemotherapy followed by maintenance avelumab in combination with talazoparib in patients with locally advanced or metastatic ovarian cancer, has been discontinued.

The decision stems from factors that include previously announced interim data of the JAVELIN Ovarian 100 trial, which ended in December 2018 after an independent panel determined the study would not meet its primary endpoint of progression-free survival. Therefore, those data did not support continuation of JAVELIN Ovarian PARP 100 in an unselected patient population.

Although safety was not a deciding factor, additional reasons for terminating the trial included recently approved treatment options for patients with ovarian cancer, including the December 2018 FDA approval of olaparib as a maintenance treatment for patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to frontline platinum-based chemotherapy.

The companies, which emphasized a need to better understand the role of immunotherapy in ovarian cancer, have notified health authorities as well as study investigators of the decision to end the study. This discontinuation does not affect current indications of avelumab nor the rest of the ongoing JAVELIN clinical development program.

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

The FDA has proposed amendments to key policies to modernize breast cancer screening and improve mammography services to enable healthcare providers and patients to make more informed medical decisions.

The proposal would modify regulations that were issued under the Mammography Quality Standards Act, which had been passed by Congress and enforced by the FDA to help ensure the delivery of high-quality mammography services.

The proposed changes were drafted to improve patient understanding of the relationship between breast density and breast cancer risk, to provide physicians with more detailed information to improve mammogram assessments, and to provide the FDA with the ability to better enforce the MQSA regulations and actively address violations.

The planned amendments also call for the distribution of more detailed information regarding the mammogram facility to both patients and providers as a way to help the post-exam process run more smoothly.

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

This week, we sat down with Dr Richard Finn, of UCLA Geffen School of Medicine, and Dr Anthony El-Khoueiry, of USC Keck School of Medicine, who discussed the future treatment paradigm of hepatocellular carcinoma.

That’s all for today.

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