September 18, 2017
By Alex Keown, BioSpace.com Breaking News Staff
BASEL, Switzerland – Two Roche drugs have been placed on partial clinical hold by the U.S. Food and Drug Administration as the regulatory agency continues to examine potential dangers of checkpoint inhibitors following deaths associated with Merck ’s Keytruda earlier this summer.
Roche is 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 Tecentriq have been placed on partial clinical hold. The FDA has requested the hold on a Phase Ib and a Phase Ib/II trial that combines Tecentriq with lenalidomide or pomalidomide 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/PDL1 medicine in combination with an immunomodulatory medicine to determine if it is a class-wide (anti-PD1/PDL1) concern in multiple myeloma/blood cancers or a specific concern with certain combinations with immunomodulatory medicines,” Roche said in a statement issued Friday.
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 has the FDA so concerned.
The FDA notified Roche about a week after the agency placed three Bristol-Myers Squibb trials on clinical holds. Trials using that company’s checkpoint inhibitor Opdivo to treat the patients with relapsed or refractory multiple myeloma were placed on hold. Two of the trials, CheckMate-039 and CA204142, are both in Phase I, while CheckMate-602 is in Phase III.
Hours after BMS reported its partial trial hold, Celgene also announced that six of its trials were also placed on full or partial holds. Celgene’s trials were all studying Imfinzi (durvalumab), 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 Keytruda 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 Keytruda arm. Each of the trials is testing Merck’s drug as a combination treatment for the blood cancer multiple myeloma. In the trials, Keytruda was being tested in combination with drugs developed by Celgene (CELG), including Pomalyst and Revlimid.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 Keytruda (pembrolizumab) was combined with other drugs.
“… the agency 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,” the FDA said in its statement.
