FDA Approval in TGCT, Breakthrough Designation in Melanoma, and More

Kristi Rosa



Today-

An FDA approval in tenosynovial giant cell tumor, a breakthrough therapy designation in melanoma, and encouraging findings in trials in bladder cancer, lung cancer, and a cell-free DNA assay.

Welcome to OncLive News Network! I'm Kristi Rosa.

The FDA has approved pexidartinib, known by the trade name Turalio, for the treatment of adult patients with symptomatic tenosynovial giant cell tumor that is associated with severe morbidity or functional limitations and not responsive to improvement with surgery.

The approval of the small molecule, CSF1R receptor inhibitor was based on findings from the phase III ENLIVEN study, which demonstrated a 38% overall response rate with pexidartinib compared with 0% with placebo following 25 weeks of treatment based on central review of MRI scans.

Additional data showed that the complete response rate was 15% and the partial response rate was 23%. The median duration of response was not reached with pexidartinib and not available with placebo. Ninety-six percent of patients had a DOR of at least 6 months, and 50% of patients had a DOR of at least 12 months.

At a median 6 months of follow-up, no responders in the trial progressed. Tumor response was assessed by tumor volume score, which was 56% with pexidartinib and 0% with placebo. Responses also correlated with improved patient symptoms and function.

TGCT is a nonmalignant tumor of the joint or tendon sheath. The disease can be locally aggressive and debilitating and is associated with severe morbidity or function limitations.

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In melanoma, the FDA granted a breakthrough therapy designation to the combination of bempegaldesleukin and nivolumab for the treatment of patients with previously untreated unresectable or metastatic disease.

The designation is based on results from a cohort of the ongoing phase I/II PIVOT-02 trial, in which the combination led to an overall response rate of 53% by independent radiology review, which included a 34% complete response rate, in this patient population.

Updated findings that were presented at the 2019 ASCO Annual Meeting showed a disease control rate was 74%. In PD-L1-positive, PD-L1-negative, and PD-L1-unknown tumors, the ORRs were 62%, 43%, and 33%, respectively. There was a 100% reduction in target lesions in 42% of patients.

Moreover, at a median 12.7 months of follow-up, 80% of patients had an ongoing response. The median duration of response was not reached, the median time to response was 2.0 months, and the median maximum reduction from baseline was -55%.

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The addition of atezolizumab to platinum-based chemotherapy significantly improved progression-free survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma, according to results from the phase III IMvigor130 study.

In the phase III IMvigor130 study, 1213 patients with locally advanced or mUC who had not received prior treatment for advanced or metastatic disease were enrolled. Patients were randomized to receive atezolizumab alone; atezolizumab combined with platinum-based chemotherapy of gemcitabine with either cisplatin or carboplatin; or the same chemotherapy option combined with placebo.

Additionally, reports showed that a positive trend in the coprimary endpoint of overall survival was noted at the interim analysis, but the data are not yet mature. No new safety signals were reported with the atezolizumab combination as compared with historical data.

The IMvigor130 data are expected to be presented at an upcoming medical conference.

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In non-small cell lung cancer, treatment with afatinib followed by osimertinib led to a median overall survival of 41.3 months and a 2-year OS rate of 80% in patients with EGFR T790M-positive disease in a real-world setting, as seen in updated interim results of the phase III GioTag study.

Moreover, in patients with exon 19 deletion-positive tumors, the median OS was 45.7 months and the 2-year OS rate was 82%. The median time on treatment for sequential afatinib and osimertinib was 28.1 months, and 30.6 months in those with Del19. Following treatment with afatinib, the median time on osimertinib was 15.6 months overall and 16.4 months for those with Del19.

The updated median time-to-treatment failure with afatinib and osimertinib was 28.1 months. In patients with Del19-positive tumors, the median TTF was 30.6 months.

A final analysis planned for early 2020 will include updated data from Asian and European countries.

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Results of an analysis showed that cell-free DNA based detection of microsatellite instability status was found to be highly concordant with tissue-based MSI testing.

Findings showed that incorporating MSI detection into the 74-gene panel liquid biopsy assay Guardant360 demonstrated high concordance in approximately 1145 cfDNA samples for which MSI status based on standard tissue testing was available.

cfDNA MSI evaluation was linked with high specificity, precision, and sensitivity, with a limit of detection of 0.1% tumor content. In 949 unique evaluable patients, cfDNA testing accurately detected 87% of patients reported as having MSI-H tumors, and 99.5% of those having microsatellite stable disease, leading to an overall accuracy rate of 98.4%; the positive predictive value was 95%.

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This week, we sat down with Dr. D. Ross Camidge, of University of Colorado Cancer Center, to discuss targeting BRAF in non-small cell lung cancer.

That's all for today.

Thank you for watching OncLive News Network! I'm Kristi Rosa.
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