ESMO: Early days, but Amgen's BiTE drug in prostate cancer shows encouraging activity

Amgen’s test for advanced prostate cancers has shown encouraging signs in an early trial, and it hopes to move past the limited efficacy seen in other immune therapies for the disease. 

In blood cancers, bispecific T-cell engager (BiTE) therapies are hoping to show superior efficacy to traditional antibodies while having easier administration methods and fewer side effects than CAR-Ts, the more well-known next-gen immuno-oncology treatment.

With AMG 160, however, Amgen is not targeting blood cancers but solid tumors, where CAR-Ts have struggled to make an impact, and going beyond its approved bispecific immunotherapy Blincyto (blinatumomab), which treats leukemia.

AMG 160, a half-life extended, PSMA-targeted BiTE, works as an immune therapy that redirects T cells to kill tumor cells by binding to PSMA on tumor cells and CD3 on T cells.

In its phase 1 test, with some initial data presented today at the 2020 European Society for Medical Oncology (ESMO) Virtual Congress, its focus is on metastatic castration-resistant prostate cancer (mCRPC).

The primary objectives of the open-label, ascending, multiple-dose trial are to test safety and tolerability as well as to find the maximum tolerated dose (MTD), or the recommended phase 2 dose of AMG 160 in men with mCRPC.

Secondary objectives are to suss out pharmacokinetics and evaluate early efficacy, with a second cohort also combining the drug with Merck’s major cancer blockbuster Keytruda, a checkpoint inhibitor.

Breaking it down, the data shown at ESMO today show that, overall, 68.6% of patients showed any PSA decline across all monotherapy dose cohorts, and among the 15 patients with measurable disease, three partial responses (PRs), with two confirmed, and eight stable disease were observed.

MTD has not been yet reached, and “dosing optimization of AMG 160 continues.” The combo of AMG 160 and Keytruda is still “in progress,” with data not yet being shared.

“We’re still very early on with this drug, it’s only been in the clinic for a year, but despite being early days, we’re 100% encouraged by the data we’re already seeing,” said Gregory Friberg, vice president and therapeutic area head at Amgen.

“Whenever you judge a data set, you have to judge it in terms of who the patients were,” he told Fierce Biotech ahead of the ESMO data drop. “Here, the patients were fifth and sixth-line, metastatic, castrate-resistant prostate cancer patients. So there were no longer being helped by a line of other therapies; in many ways, they were men who had ran out of options.”

Friberg said that seeing nearly 70% of patients across the phase 1 having some level of prostate-specific antigen (PSA) reduction (where PSA is a common measurement and can be elevated by prostate cancer cells) was a positive result.

And around a third of those had a 50% reduction of PSA. “Those kinds of numbers are quite impressive in a highly pretreated group,” Friberg said. “And it’s important to remember that we’re not done; we are continuing to optimize not only with dose priming but also our target dose. So we think that, for a first ask in a dose-escalation phase 1, this is quite promising.”

As with any immune-system-stimulating strategy, safety is a major factor, with cytokine release syndrome (CRS)—an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction—the most common safety concern.

In the phase 1, CRS of all grades were seen in more than 90% of patients (39 in all), with a quarter of those at grade 3. Amgen said, however, that there were no grade 4 or 5s, with 4 more serious and 5 a death, and that “CRS was reversible, manageable, most severe in cycle 1 and associated with fever, hypotension, transient transaminitis nausea/vomiting and/or diarrhea.”

While manageable, the CRS levels were high, and asking questions over its safety was “reasonable,” said Friberg.

“We’re continuing to learn about the BiTE platform [in terms of safety],” he said. “When you activate the immune system, that can be a powerful tool to fight the tumor, but also comes with some baggage.

“CRS is something we’re hoping we can optimize and get those levels down moving forward.”