FDA puts hold on AZ and Celgene immunotherapy trials

FDA building

Celgene and AstraZeneca are the latest companies affected by the FDA’s investigation into safety of cancer immunotherapies, after it halted one trial and stopped recruitment to five others.

Trials are testing Imfinzi (durvalumab), AstraZeneca’s anti PD-L1 antibody, combined with Celgene’s immunomodulatory and chemotherapy agents in blood cancers such as multiple myeloma, chronic lymphocytic leukaemia and lymphoma.

The FDA has been reviewing safety of antibodies targeting PD-1 and PD-L1 after data from two trials of Merck & Co’s Keytruda (pembrolizumab) in multiple myeloma showed excess deaths in patients receiving the immunotherapy drug in combination with agents such as Celgene’s Revlimid (lenalidomide) and Imnovid (pomalidomide).

No similar findings have been observed in Celgene’s FUSION programme, but the holds announced in a joint statement from the companies allow for additional information to be collected and safety risks assessed.

The FDA has already put three trials of Bristol-Myers Squibb’s Opdivo (nivolumab) on partial clinical hold, which tested the immunotherapy in combination with the Celgene drugs.

Patients already on five trials on partial clinical hold who are receiving clinical benefit will remain on treatment.

Those on the trial on full clinical hold will be have their treatment stopped and no new patients will be enrolled into the affected trials.

Other trials with Imfinzi in blood cancer and other tumour types continue unchanged.

The trials on clinical hold are:

MEDI4736-MM-001, a phase 1b study testing recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide with or without low-dose dexamethasone in patients with relapsed and refractory multiple myeloma;

MEDI4736-MM-003, a phase 2 study to determine the safety and efficacy for the combination of durvalumab and Janssen’s Darzalex (daratumumab) in patients with relapsed and refractory multiple myeloma;

MEDI4736-MM-005, a phase 2 study of durvalumab plus daratumumab in patients with relapsed and refractory multiple myeloma that have progressed while on current treatment regimen containing daratumumab;

MEDI4736-NHL-001, a phase 1/2 study assessing the safety and tolerability of durvalumab as monotherapy and in combination therapy in subjects with lymphoma or chronic lymphocytic leukaemia. The only arm in this trial for which enrolment is suspended is an arm with a durvalumab, Revlimid and rituximab combination;

MEDI4736-DLBCL-001, a phase 2 study of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or with lenalidomide plus R-CHOP (R2 CHOP) in patients with previously untreated, high risk diffuse large B Cell lymphoma.

The trial on full clinical hold is MEDI4736-MM-002, a phase Ib study to determine the recommended dose and regimen of durvalumab in combination with lenalidomide with and without low-dose dexamethasone in subjects with newly diagnosed multiple myeloma.

Two other trials on the FUSION programme, MEDI4736-MDS-001, and CC-486-MDS-006, which involve durvalumab in combination with drugs from other classes, will continue unaffected.

The FUSION programme began in April 2015, when Celgene entered into a strategic collaboration with AZ's MedImmune unit to develop and commercialise durvalumab for haematologic malignancies.

The use of durvalumab in combination with other agents for the treatment of patients blood cancer have not approved by the FDA, and the safety and efficacy of the combinations have not been established.