New Drug Approvals Highlight Week in Oncology News

Top news of the week in cancer drug development.

FDA Approves NovoTTF for Upfront GBM

The FDA has approved the NovoTTF-100A System in combination with adjuvant temozolomide as a treatment for patients with newly diagnosed glioblastoma multiforme following surgery, chemotherapy, and radiation therapy, based on an improvement in survival in the EF-14 trial. In a full analysis of 695 patients enrolled in the phase III EF-14 study, the median overall survival was 19.4 months compared with 16.6 months with temozolomide alone.

Additionally, progression-free survival was improved by approximately 3 months, according to the FDA. After a minimum follow-up of 18 months, the risk of progression or death was reduced by 37% with the addition of NovoTTF to temozolomide. The median PFS was 7.1 months with the combination compared with 4.0 months with temozolomide alone (HR, 0.63; P = .001).

Approximately half of the patients who used the device experienced some form of skin irritation. The FDA initially approved NovoTTF in 2011 as a monotherapy for adult patients with GBM that recurred or progressed after chemotherapy.

The agency reviewed the extended indication under its priority review program. With the expanded approval, the system can be used as part of a standard upfront treatment for GBM in combination with temozolomide, which is a standard adjuvant therapy. The approval was preceded just 3 days prior by an initial public offering for Novocure, the company that manufacturers the device.

See more at: http://www.onclive.com/web-exclusives/fda-expands-novottfs-gbm-indication

Pembrolizumab Approved for PD-L1—positive NSCLC

The FDA granted an accelerated approval to pembrolizumab as a treatment for patients with pretreated advanced PD-L1—expressing non–small cell lung cancer across all histologies, based on objective response rates seen in the phase I KEYNOTE-001 study. The PD-1 inhibitor was approved along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, and is indicated for patients who progressed on or after platinum-containing chemotherapy or an EGFR- or ALK-targeted therapy.

Dako manufactures the companion diagnostic in partnership with Merck. This approval marks the first for a PD-1 inhibitor specifically in patients with PD-L1—expressing tumors.

In the pivotal single-arm KEYNOTE-001 trial, the ORR with pembrolizumab was 41% among a subgroup of 61 patients with pretreated PD-L1—positive advanced NSCLC as determined by the 22C3 pharmDx diagnostic test. Response duration ranged from 2.1 to 9.1 months.

The ORR for the entire study population was nearly 20%. A survival improvement has yet to be demonstrated, and the accelerated approval is contingent upon the eventual outcomes of confirmatory studies. Pembrolizumab was approved for metastatic melanoma in 2014, based on data from another group of patients treated in the KEYNOTE-001 study. This approval is also pending phase III results.

See more at: http://www.onclive.com/web-exclusives/fda-approves-pembrolizumab-for-lung-cancer

FDA Approves Nivolumab/Ipilimumab Combo for Melanoma

The FDA has granted an accelerated approval to the combination of nivolumab and ipilimumab as a treatment for patients with BRAF V600 wild-type unresectable or metastatic melanoma, based on findings from the phase II CheckMate-069 study. In the double-blind study, the PD-1 inhibitor nivolumab plus the CTLA-4 inhibitor ipilimumab reduced the risk of progression or death by 60% compared with ipilimumab alone (HR, 0.40; 95% CI, 0.22-0.71; P <.002).

Median PFS was 8.9 months in the nivolumab/ipilimumab group versus 4.7 months in the ipilimumab arm. With the combination, the objective response rate was 60% compared with 11% with ipilimumab alone in patients with BRAF wild-type melanoma.

The accelerated approval marks the first for an immunotherapy combination for patients with cancer, with an application for full approval pending with the FDA. This submission was based on the phase III CheckMate-067 study, which showed a 59% reduction in the risk of progression or death with the combination versus ipilimumab alone (HR, 0.41; 95% CI, 0.32-0.53).

The FDA is scheduled to make a decision on this application by January 23, 2016.

See more at: http://www.onclive.com/web-exclusives/fda-approves-nivolumabipilimumab-combination-for-braf-wild-type-melanoma

FDA Grants Rociletinib a Priority Review in NSCLC

The FDA has granted a priority review designation to rociletinib for patients with EGFR T790M-mutant metastatic non—small cell lung cancer following prior administration of an EGFR TKI, based on data from the ongoing phase I/II TIGER-X trial. In patients with T790M-mutant NSCLC who received rociletinib at the 500 mg dose (n = 48), the objective response rate was 60% and the disease control rate was 90%.

The FDA received data from the TIGER-X trial under a rolling submission, which was allowed as part of a breakthrough therapy designation received in May 2014. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the application by March 30, 2016.

In addition to TIGER-X, data for rociletinib were submitted from the single-arm phase II TIGER-2 trial. Data from this study have not yet been announced, with the first patient enrolled in June 2014.

Qiagen’s therascreen EGFR RGQ PCR Kit is anticipated to be a companion diagnostic for rociletinib. This test is approved as a CDx for afatinib and gefitinib. Additionally, plasma-genotyping of T790M is under exploration using Sysmex's BEAMing system, which uses emulsion PCR and hybridization followed by flow cytometry. It is unclear which test will ultimately be the CDx of choice.

See more at: http://www.onclive.com/web-exclusives/fda-grants-priority-review-to-rociletinib-for-t790m-positive-nsclc

Eribulin Granted Priority Review for STS

The FDA has granted a priority review designation to eribulin as a treatment for patients with advanced soft tissue sarcoma following chemotherapy, based on an extension in overall survival with the microtubule dynamics inhibitor compared with dacarbazine in the phase III Study 309 trial. Pretreated patients with intermediate- and high-grade leiomyosarcoma or adipocytic sarcoma experienced a median OS with eribulin of 13.5 months compared with 11.5 months for dacarbazine, representing a 23% reduction in the risk of death (HR, 0.77; P = .0169).

The median OS in patients with the ADI subtype was 15.6 months with eribulin (n = 75) compared with 8.4 months with dacarbazine (n = 78; HR, 0.51; 95% CI, 0.35-0.75). In the LMS group, patients treated with eribulin (n = 152) had a median OS of 12.7 versus 13 months with dacarbazine (n = 145; HR, 0.93; 95% CI, 0.71-1.20).

Findings from the open-label Study 309 trial were presented at the 2015 ASCO Annual Meeting, and represented the first phase III study to show an OS improvement for patients with soft tissue sarcoma. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the application before March 30, 2016.

See more at: http://www.onclive.com/web-exclusives/fda-grants-priority-review-to-eribulin-for-soft-tissue-sarcoma

FDA Schedules Advisory Meeting for MCNA in Bladder Cancer

The FDA has scheduled an advisory hearing to discuss the biologics license application for the immunotherapy MCNA as a treatment for patients with high-risk non-muscle invasive bladder cancer following first-line bacillus Calmette-Guérin therapy. The joint committee meeting is scheduled for November 18, 2015, and will include input from ODAC and the Cellular, Tissue and Gene Therapies Advisory Committee.

The BLA for MCNA was based on findings from an open-label phase III trial, which demonstrated significant activity with MCNA, an immunotherapy that is comprised of mycobacterial cell wall fragments complexed with nucleic acids. In the study, 25% of patients treated with MCNA remained disease-free at 1-year, which met the criteria established for the primary endpoint of the study.

At 2-years, the disease-free survival rate was 19%. In patients with papillary only tumors, the DFS rate was 35.1% and 32.2% at 1 and 2 years, respectively. In late August, the FDA granted a priority review to MCNA for patients with high-risk non-muscle bladder cancer.

The agency is currently scheduled to act on the BLA for MCNA by February 27, 2016. When accepting the submission, the FDA had announced plans to schedule an advisory meeting.

See more at: http://www.onclive.com/web-exclusives/fda-schedules-advisory-meeting-for-mcna-in-bladder-cancer