3:00 PM
 | 
Dec 04, 2018
 |  BC Extra  |  Clinical News

New BCMA-targeted therapies could help sicker patients

Oral abstracts at this year’s American Society of Hematology meeting describing next generation anti-BCMA CARs from Poseida Therapeutics Inc. and Fred Hutchinson Cancer Research Center and a bispecific antibody from Amgen Inc. (NASDAQ:AMGN) hint that the improvements offered by the products will help the class treat patients who are sicker or more vulnerable to toxicities.

Amgen presented first-in-human data for AMG 420, a bispecific T cell engager (BiTE) antibody construct targeting BCMA (tumor necrosis factor receptor superfamily member 17; TNFRSF17; CD269) and CD3. Responses were seen in seven of 10 (70%) relapsed or refractory multiple myeloma patients who received the maximum tolerated dose (MTD) of 400 µg/day.

There were four deaths in the study, two from disease progression, one from hepatitis related to adenoviral infection and one from acute respiratory distress due to concurrent flu and Aspergillus infections. None were considered related to AMG 420.

That response rate is somewhat lower than the 80% or higher reported among early trials of anti-BCMA CAR T therapies (see “Assessing the BCMA Scene”).

But Amgen SVP of Global Development Elliot Levy said physicians may have steered patients at higher risk of progression towards Amgen’s trial rather than anti-BCMA CAR T trials because it can take up to four weeks to produce a CAR T product. “They enroll the sickest patients in the BiTE trials. To receive CAR T therapy, a patient has to be stable enough to wait out the production period,” he said.

Amgen plans to start a Phase Ib trial of AMG 420 in 1Q19.

Another anti-BCMA therapy with data at ASH could be safer than more advanced CAR T products.

Response rates ranged from 43-100% among dose groups in a dose-escalation Phase I trial of P-BCMA-101 from Poseida (San Diego, Calif.) in patients with relapsed or refractory MM. All three patients who received the planned Phase II dose responded.

P-BCMA-101 is an anti-BCMA CAR T cell therapy that incorporates a Centyrin-binding domain and a safety switch which, according to the company, has not yet been employed in any patient (see “Piggyback Car Ride”).

Poseida’s piggyBac technology preferentially transduces stem cell memory T cells (TSCM), which the company believes could lead to better efficacy with greater persistence of the CAR T cells and lower toxicity through more gradual tumor killing.

P-BCMA-101 also led to low rates of toxicity: cytokine release syndrome (CRS) occurred in two patients (9.5%) and did not reach grade 3 or above. There was one case of grade 3 neurotoxicity.

Poseida plans to begin a registrational trial of P-BCMA-101 next half and hopes to submit a BLA to FDA by the end of 2020.

And Fred Hutchinson Cancer Research Center’s FCARH143 showed responses in a Phase I trial in heavily pretreated relapsed or refractory MM patients. FCARH143 is an anti-BCMA CAR T cell therapy that contains CD4+ and CD8+ T cells in roughly equal proportion.

All 11 patients in the trial responded; two had relapsed at the time of the presentation. The median number of prior regimens was 11 and included prior autologous or allogeneic stem cell transplants, and one patient had previously received a CAR T cell therapy.

Fred Hutchinson is developing FCARH143 in collaboration with the NCI and the Juno Therapeutics Inc. subsidiary of Celgene Corp. (NASDAQ:CELG).

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