FDA Action Alert: G1, TG and Bristol Myers Squibb and Exelixis


The U.S. Food and Drug Administration (FDA) has several solid PDUFA dates in the middle of February. Here’s a look.

G1 Therapeutics’ Trilaciclib for Small Cell Lung Cancer

G1 Therapeutics had a target action date of February 15, 2021, for its New Drug Application (NDA) for Trilaciclib for small cell lung cancer. It was granted Priority Review. The company inked a three-year co-promotion deal for the drug in the U.S. and Puerto Rico with Boehringer Ingelheim in June 2020.

On February 12, the FDA approved the drug under the brand name Cosela.

“The approval of Trilaciclib (Cosela) is an important advance in the treatment of patients with extensive-stage small cell lung cancer receiving chemotherapy,” said Jeffrey Crawford, Geller Professor for Research in Cancer in the Department of Medicine and Duke Cancer Institute. “The most serious and life-threatening side effect of chemotherapy is myelosuppression, or damage to the bone marrow, resulting in reduced white blood cells, red blood cells and platelets. Chemotherapy-induced myelosuppression may lead to increased risks of infection, severe anemia, and/or bleeding.”

Trilaciclib is a first-in-class FDA-designated “Breakthrough Therapy.” It is currently up for NDA review for SCLC patients being treated with chemotherapy. Until FDA approval, the company is making the drug available to SCLC patients in the U.S. who can’t otherwise enter clinical trials and for whom there are no other appropriate treatments. This is under the FDA’s expanded access program (EAP).

In addition to SCLC, the drug is being evaluated across a range of tumor types and chemotherapy regimens, including in colorectal cancer and metastatic triple-negative breast cancer.

On December 9, 2020, the company reported final data from its Phase II trial of Trilaciclib in metastatic triple-negative breast cancer. The drug demonstrated significantly improved overall survival (OS) for patients receiving the drug in combination with a chemotherapy regimen of gemcitabine/carboplatin (GC) compared to GC alone.

TG Therapeutics’ Umbralisib in Marginal Zone Lymphoma

TG Therapeutics had a target action date of February 15 for its NDA for umbralisib for marginal zone lymphoma (MZL). It also had a target action date of June 15, 2021, for the same drug under standard review for follicular lymphoma.

In the results of the Phase IIb UNITY-NHL trial, the drug was evaluated alone and in combinations for patients with previously treated Non-Hodgkin’s Lymphoma (NHL). In addition to MZL and FL, it was evaluating the drug in small lymphocytic lymphoma (SLL). The MZL cohort enrolled adults with at least one previous line of therapy that included an anti-CD20 monoclonal antibody. In February 2019, the MZL cohort hit the primary endpoint of overall response rate (ORR) as determined by an Independent Review Committee (IRC) for all treated patients. The hit a target guidance of 40-50% ORR. The FDA had granted the drug Breakthrough Therapy Designation for adults with MZL who had at least one previous anti-CD20 regimen. In April 2019, the FDA also granted it orphan drug designation for patients with any of the three types of marginal zone lymphoma: nodal, extranodal, and splenic MZL. Because of the Breakthrough Therapy designations for MZL, it was granted Priority Review for that indication, with standard review for the FL.

On February 5, 2021, the FDA granted accelerated approval of umbralisib under the brand name Ukoniq for adults with relapsed or refractory marginal zone lymphoma after at least one prior anti-CD20 based regimen. It is also approved for adults with r/r FL after at least three prior lines of systemic therapy. It is the first and only inhibitor of PI3K-delta and CK1-epsilon for those indications.

Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics stated, “Today’s approval of Ukoniq marks a historic day for our company with this being our first approval and we are extremely pleased to be able to bring our novel inhibitor of PI3K-delta and CK1-epsilon to patients with relapsed/refractory MZL and FL. We have built a commercial team with significant experience who will immediately start to engage our customers to educate them on Ukoniq and how to access the product for patients in need and expect to make Ukoniq available to U.S. distributors in the next few days.”

Bristol Myers Squibb and Exelixis’ Opdivo-Cabometyx for Renal Cell Carcinoma

Bristol Myers Squibb and Exelixis had a target action date of February 20 for its supplemental Biologics License Application (sBLA) and supplemental NDA, respectively for Opdivo (nivolumab) in combination with Cabometyx (cabozantinib) for patients with advanced renal cell carcinoma (RCC). The FDA approved the combination on January 22.

“At Bristol Myers Squibb, we are focused on developing transformative medicines that may improve survival for people living with cancer,” said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, for Bristol Myers Squibb. “The role of Opdivo + Yervoy is well established for intermediate /poor-risk patients with advanced RCC, and today’s achievement extends the potential of an Opdivo-based combination to even more patients.. Opdivo in combination with Cabometyx brings together the strong heritage of both medicines to now provide physicians a new combination in advanced RCC that may offer improved outcomes to patients for whom an immunotherapy plus tyrosine kinase inhibitor regimen is appropriate.”

On February 9, the two companies announced new analysis from the Phase III CheckMate -9ER clinical trial. The study looked at the combination of BMS’s checkpoint inhibitor Opdivo (nivolumab) and Exilixis’ Cabometyx (cabozantinib) compared to Pfizer’s Sutent (sunitinib) in first-line treatment of advanced renal cell carcinoma (RCC). The data showed clinically meaningful, sustained efficacy benefits in addition to quality-of-life improvements.

The data analysis had a median follow-up of two years. In the analysis, the Opdivo-Cabometyx combo showed superior progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) compared to sunitinib. There was also a low rate of treatment-related adverse events (TRAEs) that led to discontinuation of the trial. No new safety signals were observed.

In a separate analysis than the CheckMate -9ER trial that was run with 18.1 months of median follow-up, patients who received the combination reported statistically significant quality-of-life benefits associated with health. This included lower treatment burden, decreased risk of deterioration and a decrease of disease-related symptoms compared to sunitinib. They were evaluated using Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), a quality-of-life tool used specifically in kidney cancer. It also utilized EQ-5D-3L instruments—a system made up of five dimensions, mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension includes three levels: no problems, some problems, and extreme problems.

“There is a continued need for new therapies that show benefit across subgroups of patients with advanced renal cell carcinoma,” said Robert Motzer, Kidney Cancer Section Head, Genitourinary Oncology Service, and Jack and Dorothy Byrne Chair in Clinical Oncology, Memorial Sloan Kettering Cancer Center. “In CheckMate -9ER, nivolumab in combination with cabozantinib doubled progression-free survival, increased overall survival and response rate and, in an exploratory analysis, showed impressive disease control, and these promising efficacy results were sustained with extended follow-up. Also of note, patients in this study reported significant quality-of-life improvements, which are important for patients undergoing treatment for this challenging disease.”

Most Read Today

Back to news