Priority Review in RET Fusion+ NSCLC and Thyroid Cancers, Breakthrough Status in MDS, and More


A priority review designation in RET fusion—positive lung cancer and thyroid cancers, a breakthrough therapy designation in myelodysplastic syndromes, a new drug application submitted in hepatocellular carcinoma, an ODAC meeting scheduled in lung cancer, and encouraging findings in gastric cancer and prostate cancer.

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

The FDA has granted a priority review designation to a new drug application for selpercatinib for the treatment of patients with advanced RET fusion—positive non–small cell lung cancer, RET-mutant medullary thyroid cancer, and RET fusion–positive thyroid cancer.

The NDA is based on findings from the phase I/II LIBRETTO-001 trial, which evaluated selpercatinib in RET-altered NSCLC and thyroid cancers. In the NSCLC study cohort of patients who received prior therapy, the agent demonstrated an objective response rate of 68%, including a 2% complete response rate and a 66% partial response rate; the stable disease rate was 26%. In treatment-naïve patients, the ORR with selpercatinib was 85%.

In the group of patients with RET-mutant MTC who received prior treatment with cabozantinib or vandetanib, which was known as the primary analysis set, the ORR with selpercatinib was 56%. Moreover, the CR rate was 6%, the PR rate was 51%, and 5% of patients developed progressive disease.

The FDA is expected to make a decision on the application in the third quarter of 2020.


In myelodysplastic syndromes, the FDA has granted a breakthrough therapy designation to the combination of APR-246 and azacitidine for the treatment of patients with a susceptible TP53 mutation.

A small, phase Ib trial previously examined this combination in hypomethylating agents—naïve patients with TP53-mutant MDS and oligoblastic acute myeloid leukemia. Intravenous APR-246 was given daily in a 3+3 dose-escalation design in a lead-in phase followed by the same dose combined with azacitidine.

Results showed that the objective response rate by International Working Group 2006 criteria was 100%, which included 4 complete responses and 1 marrow CR. All patients who had CR achieved complete cytogenetic response. Additionally, 1 patient in CR achieved a marrow CR and partial cytogenetic response following APR-246 lead-in prior to combination therapy.

All patients in CR had high p53 positivity by immunohistochemistry at baseline, and serial next-generation sequencing with a variant allele frequency cutoff of 2% was negative in 80% of patients. The maximum-tolerated dose had not been reached.

An ongoing pivotal phase III trial will evaluate APR-246 and azacitidine as a frontline treatment for patients with TP53-mutant MDS.


A supplemental biologics license application has been submitted to the FDA for the combination of atezolizumab and bevacizumab for the treatment of patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.

The application is based on data from the phase III IMbrave150 study, which demonstrated that atezolizumab plus bevacizumab led to a 42% reduction in the risk of death versus sorafenib. The combination was also associated with a 41% reduction in the risk of disease progression or death versus sorafenib.

Moreover, the safety profile of the combination was found to be consistent with the known tolerability of each agent alone.

The FDA is reviewing the application under the Real-Time Oncology Review program, which is designed to explore a more efficient review process to ensure safe and effective therapies are made available to patients earlier.


In non—small cell lung cancer, the FDA has scheduled an Oncology Drugs Advisory Committee hearing to discuss data supporting a supplemental biologics license application for the combination of intravenous ramucirumab injection and erlotinib for the frontline treatment of patients with metastatic disease whose tumors harbor EGFR exon 19 deletion or exon 21 substitution mutations.

Findings from the phase III RELAY trial showed that the addition of ramucirumab to erlotinib led to a 41% reduction in the risk of disease progression or death versus erlotinib alone in the first-line treatment of patients with EGFR-mutant NSCLC.

At a median follow-up of 20.7 months, the median progression-free survival by investigator assessment with the ramucirumab regimen versus erlotinib alone was 19.4 months versus 12.4 months, respectively.

This benefit was observed across several patient subgroups, including those with EGFR mutations. Those who harbored exon 19 deletions experienced a median PFS of 19.6 months with the ramucirumab combination compared with 12.5 months with erlotinib. Furthermore, those with exon 21 L858R substitution mutations had a median PFS of 19.4 months versus 11.2 months with the combination versus erlotinib alone, respectively.

The meeting is scheduled for February 26, 2020.


Trastuzumab deruxtecan was found to improve overall survival versus chemotherapy in patients with heavily pretreated unresectable or metastatic HER2-positive gastric or gastroesophageal junction cancer, according to topline findings from the phase II DESTINY-Gastric01 trial.

Patients enrolled on the trial had tumors that progressed after at least 2 regimens, including trastuzumab and chemotherapy. The codevelopers of the trastuzumab deruxtecan, AstraZeneca and Daiichi Sankyo Company, Limited, reported that the antibody-drug conjugate met the primary endpoint of the trial by inducing a clinically meaningful improvement in objective response rate versus chemotherapy.

The companies also reported that the safety and tolerability data for trastuzumab deruxtecan were similar to prior findings from a phase I trial in this patient population.

Full findings from DESTINY-Gastric01 will be presented at an upcoming medical meeting. The companies also intend to discuss the data with regulatory authorities in Japan and other countries.


In prostate cancer, darolutamide plus androgen deprivation therapy led to a significant improvement in overall survival compared with placebo and ADT in patients with nonmetastatic disease, according to results from a preplanned final OS analysis of the phase III ARAMIS trial.

Previously, the study showed that the darolutamide regimen showed a statistically significant improvement in metastasis-free survival. The median MFS was 40.4 months with darolutamide/ADT and 18.4 months with placebo/ADT, leading to a 59% reduction in the risk of metastases or death.

Based on these primary findings, the FDA approved darolutamide in July 2019 for the treatment of patients with nonmetastatic CRPC.

Full results from the final analysis, which will include data on additional endpoints and a long-term safety update, will be presented at an upcoming medical meeting.

Moreover, the phase III ARASENS study is exploring darolutamide plus ADT in combination with docetaxel in approximately 1300 patients with newly diagnosed, metastatic hormone-sensitive prostate cancer.


This week, we sat down Dr Michael Wang, of The University of Texas MD Anderson Cancer Center, to discuss updates in management of mantle cell lymphoma.

That’s all for today.

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

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