August 21, 2019 - Episode 1

FDA Approvals in NTRK Fusion+ Tumors, ROS1+ NSCLC, and Myelofibrosis, and More


FDA approvals in NTRK fusion—positive tumors, ROS1-positive non—small cell lung cancer, and myelofibrosis, priority review designations in prostate cancer and mantle cell lymphoma, and a breakthrough therapy designation in chronic lymphocytic leukemia.

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

The FDA has granted an accelerated approval to entrectinib, known by the trade name Rozlytrek, for the treatment of adult and pediatric patients at least 12 years of age with solid tumors that harbor an NTRK fusion. The agent has also been approved for the agent for the treatment of adults with ROS1-positive, metastatic non—small cell lung cancer.

The NTRK fusion indication is specific to patients who have a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed on therapy or have no alternative treatments.

The approval is based on data from an integrated analysis of the phase II STARTRK-2, phase I STARTRK-1, and the phase I ALKA-372-001 trials, which demonstrated a 57% overall response rate in those with NTRK fusion—positive solid tumors. The decision is also based on results from the phase I/Ib STARTRK-NG study.

Findings from the integrated analysis showed that the responses were observed across 10 solid tumor types, including in patients with and without CNS metastases at baseline. Moreover, the intracranial ORR was 54.5%, and more than one-quarter of these patients achieving a complete response.

Additionally, pooled findings from STARTRK-2, STARTRK-1, and ALKA-372-001 showed that entrectinib demonstrated a 78% ORR and a median DOR of 24.6 months in patients locally advanced or metastatic ROS1-positive NSCLC. The IC ORR was 55.0%.


The FDA has approved fedratinib, known by the trade name Inrebic, for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis.

The approval is based on findings from the phase III JAKARTA study, which evaluated fedratinib in patients with primary or secondary disease.

Data showed that spleen response was achieved by 37% of patients who received fedratinib at the 400-mg dose compared with 1% of patients who were on placebo. Fedratinib also improved the Total Symptom Score by at least 50% when assessed from baseline to the end of cycle 6 in 40% of patients treated with the 400-mg dose of fedratinib versus 9% of those on placebo.

Safety data were also examined from the phase II JAKARTA-2 trial, which evaluated the agent in patients with myelofibrosis who were previously exposed to ruxolitinib.

The FDA approval for fedratinib comes with a Boxed Warning for serious and fatal encephalopathy, including Wernicke’s encephalopathy, and states that thiamine levels should be assessed in all patients prior to fedratinib therapy, periodically during treatment, and as clinically indicated. The agent should not be started in patients with thiamine deficiency.


In mantle cell lymphoma, the FDA has granted a priority review designation to a new drug application for zanubrutinib for the treatment of patients who have received at least 1 prior therapy.

The application is based on data from an international phase I/II trial in patients with B-cell lymphomas, a group of patients with relapsed/refractory MCL in China in a phase II trial, pooled safety data from 5 clinical trials, and nonclinical data.

In the phase I/II trial, the investigator-assessed objective response rate with zanubrutinib was 88.9%; the complete response rate was 26.7% and the partial response rate was 62.2%.

In the single-arm, open-label, multicenter, phase II Chinese trial, updated findings showed that at a median 13.9 months of follow-up, the median PFS was 16.7 months and the median duration of response was 14.0 months. The updated ORR was 84.7%, which comprised a 76.5% CR rate and an 8.2% PR rate, and ne patient had stable disease.


The FDA has granted a priority review designation to a supplemental new drug application for enzalutamide for the treatment of patients with metastatic hormone-sensitive prostate cancer.

The designation is based on results from the phase III ARCHES and ENZAMET studies. In ARCHES, the median radiographic progression-free survival in men with mHSPC was not reached with enzalutamide and was 19.45 months with placebo, translating to a 61% reduction in risk of radiographic progression or death at a median follow-up of 14.4 months.

An interim analysis of OS showed that the median OS has not been reached in either arm, with 39 deaths in the enzalutamide arm and 45 in the placebo arm. A final OS analysis will be conducted after approximately 342 deaths.

In the phase III ENZAMET trial, the 3-year overall survival rate in men with mHSPC was 80% in patients treated with enzalutamide plus standard of care compared with 72% among those who received a different nonsteroidal antiandrogen.

In the subgroup of men who received planned concurrent docetaxel, the OS rates were similar regardless of treatment. However, there was a more significant difference in survival in men who did not receive planned early docetaxel.


In chronic lymphocytic leukemia, the FDA has granted a breakthrough therapy designation to acalabrutinib.

The designation is based on findings from the interim analyses of the phase III ELEVATE-TN and ASCEND studies, which showed that acalabrutinib either as a single agent or in combination significantly reduced the risk of disease progression or death compared with standard regimens.

Regarding safety, the tolerability of the BTK inhibitor in both trials was found to be consistent with prior studies.

In ELEVATE-TN, it was announced that single-agent acalabrutinib showed a statistically significant and clinically meaningful improvement in PFS versus obinutuzumab/chlorambucil, and the company ended the trial early due to these positive data.

In ASCEND, results showed that, at a median follow-up of 16.1 months, the median PFS with acalabrutinib was not reached compared with 16.5 months for those who received rituximab/idelalisib or arms, translating to a 69% reduction in the risk of progression or death. At 12 months, 88% of patients on acalabrutinib showed no disease progression compared with 68% in the control arm.


This week, we sat down with Richard Finn, MD, of the David Geffen School of Medicine at UCLA, to discuss multidisciplinary management of hepatocellular carcinoma.

That’s all for today.

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