A Look Back at January FDA News

In January 2019, the FDA announced several approvals for patients with acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), hepatocellular carcinoma (HCC), as well as expanded an approval for patients with lung cancer. Several supplemental biologics license applications (sBLAs) were submitted this month while the FDA announced 2 breakthrough therapy designations.

Another biosimilar received approval, while the 23andMe direct-to-consumer genetic test received approval for providing a risk report related to colorectal cancer (CRC). Other updates were announced for breast and cervical cancer.

Here's a complete list of FDA news from January 2019:

Hematology Updates

Dasatinib Receives FDA Approval for Pediatric Ph+ ALL

On January 2, 2019, the FDA granted approval for dasantinib (Sprycel) as a treatment in combination with chemotherapy for pediatric patients with newly diagnosed Philadelphia chromosome-positive ALL.

"The recent approval of another tyrosine kinase inhibitor is important in the pediatric and adolescent and young adult (AYA) paradigm, as this is a class of drugs that we have been using widely for many years in adult Ph+ B-AL," Naveen Pemmaraju, MD, an associate professor in the department of leukemia at MD Anderson Cancer Center, toldTargeted Oncology. "Also importantly, this recent approval represents the continued emphasis by the field on specific clinical trials that include important subgroups of patients, as this trial included, for AYA patients who represent a unique group of patients with varying characteristics from older adult counterparts.”

Zanubrutinib Granted Breakthrough Designation From FDA for MCL

On January 14, 2019, the FDA granted a breakthrough therapy designation to zanubrutinib (BGB-3111), a BTK inhibitor, for the treatment of adult patients with mantle cell lymphoma.

The 1-year progression-free survival (PFS) rate was 90% and the 2-year PFS was 82%, according to the results from the phase II single-arm, open-label multicenter Chinese trial (NCT03206970) that the designation was based on. According to a presentation of the data at the 2018 ASH Annual Meeting, the median PFS was not yet reached at a median follow-up of 35.9 weeks.

Frontline Daratumumab Triplet Seeking FDA Approval in Multiple Myeloma

On January 22, 2019, an sBLA has been initiated with the FDA for the combination of daratumumab (Darzalex) with lenalidomide (Revlimid) and dexamethasone (DRd) for the treatment of patients with multiple myeloma who are not candidates for high-dose chemotherapy and autologous stem-cell transplant. This was based on the findings from the phase III MAIA study.

DRd reduced the risk of disease progression or death by 44% compared to patients who received lenalidomide plus dexamethasone (Rd) alone. The median PFS had also not yet been reached at a 28-month follow-up versus 31.9 months in the Rd arm.

Umbralisib Receives Breakthrough Designation from FDA for Marginal Zone Lymphoma

The FDA granted umbralisib (TGR-1202) a breakthrough therapy designation on January 22, 2019, for the treatment of adult patients with marginal zone lymphoma (MZL) who have received 1 prior anti-CD20 regimen.

Ibrutinib Plus Obinutuzumab Approved by FDA as Frontline CLL/SLL Treatment

The FDA approved the combination ibrutinib (Imbruvica) plus obinutuzumab (Gazyva) on January 28, 2019, for the treatment of patients with CLL or SLL as a first-line regimen. This approval was based ondata from the iLLUMINATE (PCYC-1130) trial.

“We already know that ibrutinib single-agent has already been approved and the obinutuzumab has also been approved in combination with chlorambucil,” said Carol Moreno, MD. However, data from this trial demonstrated “the combination of ibrutinib plus obinutuzumab resulted in superior progression-free survival (PFS) compared to conventional chemoimmunotherapy.”

“In addition to single-agent ibrutinib, the combination of ibrutinib plus obinutuzumab offers another option to achieve a long-term PFS in patients with CLL,” added Moreno, a senior staff member in the department of hematology at the Hospital de la Santa Creu Sant Pau, Autonomous University of Barcelona.

Lung Cancer Updates

FDA Accepts sBLA for Frontline Atezolizumab Triplet in Nonsquamous NSCLC

The FDA accepted an sBLA on January 17, 2019, for a triplet regimen of atezolizumab (Tecentriq), carboplatin, and nab-paclitaxel (Abraxane) as a treatment for patients with metastatic nonsquamous non—small cell lung cancer (NSCLC).

There was a statistically significant improvement in both PFS and overall survival (OS) in these patients, according to the data presented at the ESMO 2018 Congress. The FDA is expected to make a decision by September 2, 2019.

FDA Expands Pemetrexed Indication for Frontline Immunochemotherapy Combo in NSCLC

The FDA expanded its approval for pemetrexed (Alimta) injection in combination with pembrolizumab (Keytruda) and platinum-based chemotherapy to include the first-line treatment of patients with metastatic nonsquamous non—small cell lung cancer (NSCLC) without EGFR or ALK alterations. This decision, announced January 31, 2019, was based on data from the phase III KEYNOTE-189 trial.

According to a presentation of these data, the risk of death was reduced by 51% in this patient population and the median OS had not yet been reached compared to 11.3 months in the chemotherapy-alone arm.

Breast Cancer Updates

Complete Response Letter From FDA Cites Issues With Sacituzumab Govitecan in TNBC

The FDA issued a complete response letter in response to a BLA for sacituzumab govitecan as a treatment for patients with metastatic triple-negative breast cancer (TNBC) on January 18, 2019. The BLA was previously submitted based on findings from phase II results in which the agent demonstrated an objective response rate of 34% in patients with heavily pretreated mTNBC. It was granted a priority review designation in July 2018.

Third Trastuzumab Biosimilar Gains FDA Approval

On January 18, 2019, the FDA approved the third trastuzumab (Herceptin) biosimilar, SB3 (Ontruzant; trastuzumab-dttb), for the treatment of patients with HER2-overexpressing breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma. This approval, based on data from 7 clinical trials, was previously approved by the European Commission in November 2017.

Gastrointestinal Cancers

Cabozantinib Receives FDA Approval for Advanced HCC

Based on results from the phase III CELESTIAL trial, cabozantinib (Cabometyx) received approval on January 14, 2019, for the treatment of patients with HCC who previously received sorafenib (Nexavar).

“Cabozantinib is a potent agent after sorafenib, and it can be used in the second-line and third-line,” Masatoshi Kudo, MD, of Kindai University Faculty of Medicine in Osaka, Japan, told Targeted Oncology. “So far, we only had regorafenib (Stivarga) and sorafenib, so this is another option and is good for HCC patients.”

Third Trastuzumab Biosimilar Gains FDA Approval

In addition to its approval in breast cancer, this biosimilar for trastuzumab has also been approved for the treatment of patients with HER1-positive metastatic gastric or gastroesophageal junction adenocarcinoma. The approval of this biosimilar SB3 was based on data from 7 clinical trials in which the survival outcomes and safety were similar to those with trastuzumab.

Other FDA Updates

Direct-To-Consumer Test for Hereditary CRC Syndrome Approved by FDA

23andMe, a direct-to-consumer genetic test, was approved by the FDA for providing a risk report on MUTYH-associated polyposis, a hereditary CRC syndrome. Following the approval, the test will report on the 2 most common genetic variants influencing MUTHY-associated polyposis and will be available to all new and existing customers.

The FDA has previously granted 4 separate de novo authorizations to 23andMe for carrier status, genetic health risk reports, select BRCA1 and BRCA2 variants, and pharmacogenetic reports.

FDA Places Hold on Cervical Cancer Trial Evaluating AIM2CERV

On January 24, 2019, the FDA placed a partial clinical hold on the phase III AIM2CERV trial (NCT02853604). This trial is investigating the use of axalimogene filolisbac (AXAL), an immunotherapeutic agent, in patients with high-risk locally advanced cervical cancer. No new patients can enroll until the hold is resolved, but those patients who are already enrolled with continue to receive treatment.