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FDA Approvals in SCLC and of a Biosimilar, and Japanese Approvals in AML, Ovarian Cancer, and NTRK+ Tumors

Gina Columbus
Published: Monday, Jun 24, 2019



Today-

FDA approvals in small cell lung cancer and of a biosimilar, a European approval in ovarian cancer, and Japanese approvals in acute myeloid leukemia, ovarian cancer, and NTRK-positive tumors.

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

The FDA has approved pembrolizumab for the treatment of patients with metastatic small cell lung cancer who have disease progression on or after platinum-based chemotherapy and at least 1 other prior line of treatment.

The approval is based on pooled results from cohorts of the phase II KEYNOTE-158 and phase Ib KEYNOTE-028 trials. Data demonstrated that the PD-1 inhibitor elicited a 19% overall response rate in patients with SCLC who had disease progression on or after platinum-based chemotherapy and 1 or more other line of treatment.

The ORR for pembrolizumab comprised a 2% complete response rate and a 17% partial response rate. Moreover, among the 16 responding patients, 94% had a duration of response of at least 6 months, 63% had a DOR of at least 12 months, and 56% of patients had a DOR lasting longer than 18 months.

The accelerated approval for pembrolizumab is contingent on the results of a confirmatory trial.

Pembrolizumab is also being explored in combination with etoposide and platinum-based chemotherapy in patients with newly diagnosed, extensive-stage SCLC in the ongoing phase III KEYNOTE-604 study.

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The FDA has approved the trastuzumab biosimilar ABP 980, known by the trade name Kanjinti, for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, marking the fifth approval by the agency for a trastuzumab biosimilar.

Results of the phase III LILAC trial, which were presented at the 2018 ASCO Annual Meeting, showed that ABP 980 demonstrated equivalent pathologic complete response rates and similar safety findings to that of reference trastuzumab, based on central laboratory evaluation in patients with HER2-positive early breast cancer. There were no clinically meaningful differences between the two products.

The approval follows a rejection from the FDA in May 2018, when the agency rejected the biologics license application that was submitted in July 2017.

The European Commission approved ABP 980, also for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, in 2018.

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In ovarian cancer, the European Commission has approved olaparib as a single agent for the maintenance treatment of adult patients with advanced BRCA1/2-mutated germline and/or somatic high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response following first-line platinum-based chemotherapy.

The approval is based on results from the double-blind, phase III SOLO-1 study, in which maintenance olaparib led to a 70% reduction in the risk of disease progression or death versus placebo in patients with BRCA-mutant advanced ovarian cancer after completing frontline platinum-based chemotherapy. The median PFS by independent central review was not reached in the olaparib arm, versus 14.1 months in the placebo arm. The investigator-assessed PFS in the olaparib arm was not reached versus 13.8 months in the placebo arm.

The FDA approved olaparib for this indication in December 2018.

Shortly after the European approval, Japan’s Pharmaceuticals and Medical Devices Agency approved the PARP inhibitor as a maintenance treatment for patients with BRCA-mutant ovarian cancer after undergoing first-line chemotherapy, also based on the SOLO-1 data.

Olaparib is the sole PARP inhibitor that is approved for use in Japan.

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The Ministry of Health, Labor and Welfare of Japan has approved quizartinib for the treatment of adult patients with relapsed/refractory FTL3-ITD–positive acute myeloid leukemia, as detected by an MHLW-approved assay.

The approval of the second-generation FLT3 inhibitor is mostly based on the phase III findings of the QuANTUM-R trial, as well as a phase II study, which demonstrated that oral quizartinib showed a statistically significant improvement in overall survival compared with chemotherapy in this patient population.

Results showed that quizartinib led to a 24% reduction in the risk of death versus chemotherapy. The median OS was 6.2 months in patients on the quizartinib arm compared with 4.7 months in those who received salvage chemotherapy.

In May 2019, the FDA’s Oncologic Drugs Advisory Committee voted 8-3 against approving a new drug application for quizartinib for adult patients with relapsed/refractory FLT3-ITD–positive AML, after conducting its own efficacy analysis. And this week, the FDA issued a complete response letter officially denying the new drug application for quizartinib.

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

Entrectinib, known by the trade name Rozlytrek, received its first regulatory approval, as Japan’s Ministry of Health, Labour and Welfare approved the drug for the treatment of adult and pediatric patients with NTRK fusion–positive, advanced recurrent solid tumors.

The approval is based on data from the phase II STARTRK-2, phase I STARTRK-1, and phase I ALKA-372-001 trials, as well as findings from the phase I/II STARTRK-NG pediatric study.

Specifically, in STARTRK-2, entrectinib achieved an objective response rate of 56.9% in patients with NTRK-positive solid tumors, and the median duration of response was 10.4 months. Among patients with central nervous system metastases, the intracranial ORR was 50%.

Moreover, Japanese regulatory authorities are also in the process of reviewing a potential indication for entrectinib for the treatment of patients with ROS1 fusion–positive locally advanced or metastatic non–small cell lung cancer.

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

This week, we sat down with Dr Kathleen Moore, of Stephenson Cancer Center, to discuss the role of BRCA mutations in advanced ovarian 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 small cell lung cancer and of a biosimilar, a European approval in ovarian cancer, and Japanese approvals in acute myeloid leukemia, ovarian cancer, and NTRK-positive tumors.

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

The FDA has approved pembrolizumab for the treatment of patients with metastatic small cell lung cancer who have disease progression on or after platinum-based chemotherapy and at least 1 other prior line of treatment.

The approval is based on pooled results from cohorts of the phase II KEYNOTE-158 and phase Ib KEYNOTE-028 trials. Data demonstrated that the PD-1 inhibitor elicited a 19% overall response rate in patients with SCLC who had disease progression on or after platinum-based chemotherapy and 1 or more other line of treatment.

The ORR for pembrolizumab comprised a 2% complete response rate and a 17% partial response rate. Moreover, among the 16 responding patients, 94% had a duration of response of at least 6 months, 63% had a DOR of at least 12 months, and 56% of patients had a DOR lasting longer than 18 months.

The accelerated approval for pembrolizumab is contingent on the results of a confirmatory trial.

Pembrolizumab is also being explored in combination with etoposide and platinum-based chemotherapy in patients with newly diagnosed, extensive-stage SCLC in the ongoing phase III KEYNOTE-604 study.

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

The FDA has approved the trastuzumab biosimilar ABP 980, known by the trade name Kanjinti, for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, marking the fifth approval by the agency for a trastuzumab biosimilar.

Results of the phase III LILAC trial, which were presented at the 2018 ASCO Annual Meeting, showed that ABP 980 demonstrated equivalent pathologic complete response rates and similar safety findings to that of reference trastuzumab, based on central laboratory evaluation in patients with HER2-positive early breast cancer. There were no clinically meaningful differences between the two products.

The approval follows a rejection from the FDA in May 2018, when the agency rejected the biologics license application that was submitted in July 2017.

The European Commission approved ABP 980, also for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, in 2018.

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

In ovarian cancer, the European Commission has approved olaparib as a single agent for the maintenance treatment of adult patients with advanced BRCA1/2-mutated germline and/or somatic high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response following first-line platinum-based chemotherapy.

The approval is based on results from the double-blind, phase III SOLO-1 study, in which maintenance olaparib led to a 70% reduction in the risk of disease progression or death versus placebo in patients with BRCA-mutant advanced ovarian cancer after completing frontline platinum-based chemotherapy. The median PFS by independent central review was not reached in the olaparib arm, versus 14.1 months in the placebo arm. The investigator-assessed PFS in the olaparib arm was not reached versus 13.8 months in the placebo arm.

The FDA approved olaparib for this indication in December 2018.

Shortly after the European approval, Japan’s Pharmaceuticals and Medical Devices Agency approved the PARP inhibitor as a maintenance treatment for patients with BRCA-mutant ovarian cancer after undergoing first-line chemotherapy, also based on the SOLO-1 data.

Olaparib is the sole PARP inhibitor that is approved for use in Japan.

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

The Ministry of Health, Labor and Welfare of Japan has approved quizartinib for the treatment of adult patients with relapsed/refractory FTL3-ITD–positive acute myeloid leukemia, as detected by an MHLW-approved assay.

The approval of the second-generation FLT3 inhibitor is mostly based on the phase III findings of the QuANTUM-R trial, as well as a phase II study, which demonstrated that oral quizartinib showed a statistically significant improvement in overall survival compared with chemotherapy in this patient population.

Results showed that quizartinib led to a 24% reduction in the risk of death versus chemotherapy. The median OS was 6.2 months in patients on the quizartinib arm compared with 4.7 months in those who received salvage chemotherapy.

In May 2019, the FDA’s Oncologic Drugs Advisory Committee voted 8-3 against approving a new drug application for quizartinib for adult patients with relapsed/refractory FLT3-ITD–positive AML, after conducting its own efficacy analysis. And this week, the FDA issued a complete response letter officially denying the new drug application for quizartinib.

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

Entrectinib, known by the trade name Rozlytrek, received its first regulatory approval, as Japan’s Ministry of Health, Labour and Welfare approved the drug for the treatment of adult and pediatric patients with NTRK fusion–positive, advanced recurrent solid tumors.

The approval is based on data from the phase II STARTRK-2, phase I STARTRK-1, and phase I ALKA-372-001 trials, as well as findings from the phase I/II STARTRK-NG pediatric study.

Specifically, in STARTRK-2, entrectinib achieved an objective response rate of 56.9% in patients with NTRK-positive solid tumors, and the median duration of response was 10.4 months. Among patients with central nervous system metastases, the intracranial ORR was 50%.

Moreover, Japanese regulatory authorities are also in the process of reviewing a potential indication for entrectinib for the treatment of patients with ROS1 fusion–positive locally advanced or metastatic non–small cell lung cancer.

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

This week, we sat down with Dr Kathleen Moore, of Stephenson Cancer Center, to discuss the role of BRCA mutations in advanced ovarian cancer.

That’s all for today.

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