609O - Results from a phase I study of AMG 160, a half-life extended (HLE), PSMA-targeted, bispecific T-cell engager (BiTE®) immune therapy for metastatic castration-resistant prostate cancer (mCRPC)

Background

Immune therapies have offered limited efficacy in mCRPC. AMG 160 is a targeted HLE BiTE® immune therapy that engages patients’ own T cells to kill prostate cancer cells via binding of CD3 on T cells and PSMA on cancer cells. We report preliminary results from the dose exploration portion of an ongoing phase I study of AMG 160 in mCRPC.

Methods

Eligible patients (pts) had mCRPC refractory to prior novel hormonal therapy and 1–2 taxane regimens and evidence of progressive disease. AMG 160 was administered as a short IV infusion Q2W at doses of 0.003–0.9 mg. The combination of AMG 160 + pembrolizumab was also evaluated. Study objectives were to evaluate safety, tolerability, pharmacokinetics, and anti-tumor activity.

Results

As of 11 May 2020, 32 pts had received ≥ 1 dose of AMG 160 monotherapy at 6 dose levels (DL), and 16 pts were on treatment (6 for ≥ 6 mo). Median (range) age was 65.5 (49–78) y; 20 pts (63%) had received > 3 prior lines of therapy. Cytokine release syndrome (CRS), the most common adverse event (27 pts, see Table), presented with fever, transaminitis, and hypotension, occurred primarily in cycles 1–2, and was managed with standard mitigation approaches. One treatment-related discontinuation (DL5) and 2 reversible dose-limiting toxicities (DLTs) were reported: rash (DL3) and GI hemorrhage (DL6). MTD has not been reached. RECIST 1.1 responses among the 18 pts with measurable disease included 1 confirmed PR (DL4), 5 SD, and 5 PD. PSA reductions occurred in 15/24 (63%) evaluable pts; reductions >50% occurred in 6/10 (60%) pts at DL5 and DL6. Overall, 6/22 (27%) pts had confirmed PSA responses: 1 PSA90 (DL4), 3 PSA50 (DL3, DL5, DL6), 2 PSA30 (DL3, DL5). Six pts also received AMG 160 (DL3) + pembrolizumab; no DLTs were reported.

Conclusions

AMG 160 treatment was tolerable with preliminary efficacy. Further dose exploration is ongoing; results will be updated. Table: 609O

There were no fatal AEs.

Clinical trial identification

NCT03792841.

Editorial acknowledgement

Medical writing support was provided by Micah Robinson, PhD (Amgen Inc.) and Lee B. Hohaia, PharmD, CMPP (ICON plc), whose work was funded by Amgen Inc.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

B. Tran: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Tolmar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen-Cliag; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Ipsen; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck Sharp & Dohme. L. Horvath: Honoraria (self), Advisory/Consultancy, Shareholder/Stockholder/Stock options: Imagion Bioystems; Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, an immediate family member: Connected Medical Solutions ; Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas Pharma; Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen-Cilag; Travel/Accommodation/Expenses: Pfizer. T. Dorff: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Janssen Oncology; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Noxopharm; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Exelixis; Speaker Bureau/Expert testimony: Prometheus Laboratories. M. Rettig: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Johnson & Johnson; Advisory/Consultancy: Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Johnson and Johnson; Advisory/Consultancy: Ambrx ; Advisory/Consultancy: Amgen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Medication/Astellas; Licensing/Royalties, Co-inventor on a patent for novel inhibitors of the N-terminal domain of the AR: No Commercial Partners. M.P. Lolkema: Advisory/Consultancy, Research grant/Funding (institution): Johnson & Johnson; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Amgen; Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Julius Clinical. J-P. Machiels: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy: Merck Serono; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy: CUE Bioparma; Advisory/Consultancy: ALX Oncology; Travel/Accommodation/Expenses: Amgen; Research grant/Funding (self): Sanofi. S. Rottey: Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (self): Merck Sharp and Dohme; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Johnson & Johnson). K. Autio: Research grant/Funding (institution): CytomX Therapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Merck; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): ARMO BioSciences; Research grant/Funding (institution): Tizona Therapeutics, Inc; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer. R. Greil: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy: Abbvie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Gilead Sciences; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Janssen-Cilag; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution): Sandoz. N. Adra: Research grant/Funding (institution): Merck; Research grant/Funding (institution): Genentech. M. Minocha: Shareholder/Stockholder/Stock options, Full/Part-time employment: Amgen. F-C. Cheng: Shareholder/Stockholder/Stock options, Full/Part-time employment: Amgen. H. Kouros-Mehr: Shareholder/Stockholder/Stock options, Full/Part-time employment: Amgen); . K. Fizazi: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen Oncology; Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy: Sanofi; Advisory/Consultancy: Orion Pharma GmbH; Advisory/Consultancy: Curevac; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: ESSA; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen. All other authors have declared no conflicts of interest.