FDA Puts Two More Cancer Drug Trials on Partial Hold

Patient deaths related to other combination therapies concern the agency

Two cancer trials involving atezolizumab (Tecentriq, Genentech) have been placed on partial clinical hold by the FDA as the regulatory agency continues to examine potential dangers of checkpoint inhibitors following deaths associated with pembrolizumab (Keytruda, Merck) earlier this summer, according to a report from BioSpace.

Genentech is a subsidiary of Roche, which becomes the latest company to see its checkpoint inhibitor placed on hold amid concerns about increased risk of patient death when being used as a treatment for blood cancers.

Roche said two combination therapy trials with its drug atezolizumab have been placed on partial clinical hold. The FDA has requested the hold on a phase 1b and a phase 1b/2 trial that combines atezolizumab with lenalidomide (Revlimid, Celgene) or pomalidomide (Pomalyst, Celgene) to treat relapsed/refractory multiple myeloma. Roche said it will work closely with the FDA while the regulatory agency investigates. Roche said the trials placed on partial clinical hold include cohorts evaluating the combination treatments in relapsed/refractory multiple myeloma and relapsed/refractory follicular lymphoma.

“It is our understanding that the FDA is evaluating all ongoing blood cancer trials investigating an anti-PD1/PD-L1 [programmed death-1/programmed death ligand-1] medicine in combination with an immunomodulatory medicine to determine if it is a class-wide (anti-PD1/PD-L1) concern in multiple myeloma/blood cancers or a specific concern with certain combinations with immunomodulatory medicines,” Roche said in a statement.

While the Roche trials are still in early phases, the company said it has not seen any evidence concerning increased death or serious adverse events in the immuno-oncology combination trials that have the FDA so concerned.

The FDA notified Roche about a week after the agency placed three Bristol-Myers Squibb trials on clinical hold. Trials using that company’s checkpoint inhibitor nivolumab (Opdivo) to treat patients with relapsed or refractory multiple myeloma were placed on hold. Two of the trials, CheckMate-039 and CA204142, are in phase 1, while CheckMate-602 is in phase 3.

Hours after Bristol-Myers Squibb reported its partial trial hold, Celgene also announced that six of its trials were placed on full or partial holds. Celgene’s trials were all studying durvalumab (Imfinzi), an anti-PD-L1 antibody, in combination with other immune and chemotherapeutic drugs in blood cancers.

In July, the FDA placed a clinical hold on three clinical trials using pembrolizumab following the report of patient deaths in June. Merck said its Keynote-183, Keynote-185, and Keynote-023 trials were halted by the FDA after the data-monitoring committee discovered more patient deaths were observed in the pembrolizumab arm. Each of the trials is testing Merck’s drug as a combination treatment for multiple myeloma. In the trials, pembrolizumab was being tested in combination with drugs developed by Celgene, including lenalidomide and pomalidomide. Although Roche’s trials are on partial clinical hold, the company said patients who are currently enrolled and seeing clinical benefits may continue with treatments. No additional patients can be enrolled until the FDA releases the trials.

At the end of August, the FDA said it was spurred to action after researchers noted an increase of deaths when pembrolizumab was combined with other drugs. The FDA said in its statement that it is “working with sponsors of other similar cancer drugs, known as PD-1/PD-L1 inhibitors, to examine other trials in which these drugs are being studied in combination with other drugs, known as immunomodulatory agents, and in which they’re being studied in combination with other classes of drugs in hematologic malignancies. The FDA will take appropriate action as warranted to ensure patients enrolled in these trials are protected and that doctors and clinical trial researchers understand the risks associated with this investigational use.”

Source: BioSpace.com; September 18, 2017.