Early Study Results Show Novel Therapy Safe, Effective in Metastatic Castration-Resistant Prostate Cancer

Preliminary results of a phase 1 clinical trial that was presented at the virtual 2020 ESMO Congress demonstrated that a novel BiTE® immuno-oncology therapy — AMG 160 — showed a manageable safety profile, with preliminary evidence of efficacy in men with metastatic castration-resistant prostate cancer (mCRPC) who were heavily pretreated.

“Despite the long list of agents now approved for the treatment of metastatic castration-resistant prostate cancer, there remains an urgent need for treatments that can overcome resistance to hormonal therapies, chemotherapies and radiation therapies,” Dr. Ben Tran, of the Peter MacCallum Cancer Centre in Australia, said during his presentation. “And despite impressive activity in other cancers, novel immune based therapies have offered limited efficacy in mCRPC.”

Tran and colleagues aimed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of AMG 160 – a targeted half-life extended BiTE (bispecific T-cell engager) immune therapy that engages patients’ own T cells to kill prostate cancer cells by binding CD3 on T cells and prostate-specific membrane antigen (PSMA) on cancer cells.

In the global, open-label phase 1 study, the researchers plan to evaluate the safety and tolerability of AMG 160 monotherapy (part 1) or in combination with Keytruda (pembrolizumab; part 2) in men with mCRPC that is refractory to prior novel hormonal therapy and one to two taxane regimens and evidence of progressive disease.

“The study is nearing completion of the dose exploration phase 1b, followed by those expansion phase armory objectives to evaluate the safety and tolerability of AMG 160 and to determine its recommended phase 2 dose and secondary objectives to characterize pharmacokinetics and evaluate preliminary anti-tumor activity,” Tran said.

Most patients (median age, 66 years) were white (79.1%) and had received at least four prior lines of therapy (60.5%). Median PSA at baseline was 79.2 μg/L (range, 0.1-4035.0 μg/L).

Forty-three patients received one or more dose of AMG 160 monotherapy, of which 41 (95.3%) experienced treatment-emergent adverse events (TEAEs). In addition, 19 patients remained on treatment at the time of data analysis.

Forty-one patients experienced treatment-related AEs (TRAEs), including, but not limited to, cytokine release syndrome (CRS; 90.7%), fatigue (44.2%), vomiting (44.2%), nausea (39.5%), headache (34.9%), diarrhea (32.6%), dry mouth (30.2%), rash (27.9%), hypotension (23.3%), chills (23.3%), and decreased appetite (20.9%). Of note, no serious or severe events occurred, and none resulted in treatment discontinuation.

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CRS was most severe in the first cycle of therapy and was associated with fever, hypotension, nausea/vomiting and/or diarrhea. However, all instances of the side effect were reversible and manageable. There were no occurrences of serious or severe CRS events or treatment discontinuations related to the side effect.

“A number of mitigation strategies were used to improve the CRS profile of AMG 160,” Tran said. “Prophylactic mitigation was step dosing or dose priming, in which lower running doses were given prior to the maintenance target dose, which is administered every two weeks. Free medication with dexamethasone and prophylactic hydration with IV normal saline were also administered. These mitigation strategies appear to be effective in minimizing the risk of grade 3 serious events and serious adverse events.”

In total, 27.6% of patients had a confirmed PSA response to AMG 160. Overall, 68.6% of patients showed any PSA decline across all monotherapy dose cohorts and 34.3% of patients showed a greater than or equal to PSA50 reduction.

Among the 15 patients with measurable disease, three experienced a partial response and eight had stable disease. Moreover, 44.2% of patients remained on AMG 160 at the time of data analysis, with six continuing treatment for another six months or more.

Maximum tolerated dose has not been reached and dosing optimization of AMG 160 continues. Meanwhile, the investigation of AMG 160 in combination with Keytruda is in progress.

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