All times are listed in CEST (Central European Summer Time)
- Silke Gillessen (Bellinzona, Switzerland)
- Maria De Santis (Berlin, Germany)
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)
- Ben Tran (Melbourne, Australia)
Abstract
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. There were no fatal AEs.
Treatment-emergent adverse events (AEs) in > 20% of pts N = 32 All Grade Grade 3 Grade 4 n (%) n (%) n (%) CRS (Lee criteria) 27 (84.4) 10 (31.3) 0 Hypotension 8 (25.0) 4 (12.5) 0 Fatigue 18 (56.3) 3 (9.4) 0 Vomiting 17 (53.1) 1 (3.1) 0 Headache 15 (46.9) 0 0 Nausea 14 (43.8) 0 0 Pyrexia 14 (43.8) 0 0 Decreased appetite 11 (34.4) 1 (3.1) 0 Diarrhea 11 (34.4) 2 (6.3) 0 Arthralgia 10 (31.3) 1 (3.1) 0 Chills 10 (31.3) 0 0 Hypophosphatemia 10 (31.3) 3 (9.4) 1 (3.1) Back pain 9 (28.1) 1 (3.1) 0 Dry mouth 9 (28.1) 0 0 Anemia 8 (25.0) 5 (15.6) 0 Constipation 8 (25.0) 0 0 Platelet count decreased 8 (25.0) 1 (3.1) 2 (6.3) Rash 7 (21.9) 1 (3.1) 0
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.
Invited Discussant 609O
- Cora N. Sternberg (New York, United States of America)
Q&A and live discussion
- Silke Gillessen (Bellinzona, Switzerland)
611O - Abiraterone acetate plus prednisolone for hormone-naïve prostate cancer (PCa): Long-term results from metastatic (M1) patients in the STAMPEDE randomised trial (NCT00268476)
- Nicholas D. James (London, United Kingdom)
Abstract
Background
Abiraterone acetate plus prednisolone previously showed a clear survival advantage in men starting long-term hormone therapy for prostate cancer in STAMPEDE, a randomized controlled trial using a multi-arm multi-stage platform design. STAMPEDE included a wide range of men with M1 or M0 disease. The LATITUDE trial, in patients with high-burden M1 disease only, reported a similar magnitude of effect to the comparable subset of STAMPEDE pts. We report long-term outcomes in the M1 subset of pts in STAMPEDE.
Methods
All patients received androgen deprivation therapy (ADT). Stratified randomization allocated pts 1:1 to ADT alone or adding daily abiraterone acetate 1000mg + prednisolone 5mg (SOC+AAP) continued until PSA, radiological & clinical progression. The primary outcome measure was death from any cause. The data freeze for this long-term analysis was planned for 3yr after the primary survival results when a meaningful increase in data was anticipated. Analyses used Cox proportional hazards & flexible parametric models, adjusted for baseline stratification factors.
Results
Of 1,917 pts contemporaneously randomized to these groups (Nov-2011 to Jan-2014), 1,003 (52%) had M1 disease. The M1 groups were balanced: median age 67yr; 48% high-burden, 44% low-burden, 8% burden not assessable; 94% newly-diagnosed; median PSA 97ng/ml. Median follow-up had increased from 3.5yr to 6.1yr & number of ADT-only deaths increased by 50%, from 218 previously to 329. With 244 ADT+AAP deaths, the adjusted HR=0·60 (95%CI 0·50—0·71; p=0.31x10-9) favouring ADT+AAP, with 5-yr survival improved from 41% ADT-only to 60% ADT+AAP. The relative effect of abiraterone was similar in low-burden (HR=0·55; 95%CI 0·41—0·76) and high-burden (HR=0·54; 95%CI 0·43—0·69) patients. Median time on ADT+AAP was 2.4yr, with a current maximum of 8.1yr. Toxicity at 4yr post-randomisation was similar, with 16% of patients in each group reporting grade 3 or higher toxicity.
Conclusions
A sustained and substantial improvement in overall survival of M1 prostate cancer patients was achieved with ADT + abiraterone acetate + prednisolone, irrespective of burden of disease.
Clinical trial identification
NCT00268476.
Legal entity responsible for the study
UCL and the STAMPEDE investigators.
Funding
Janssen; Astellas, Clovis, Novartis, Pfizer, Sanofi Aventis.
Disclosure
N. James: Advisory/Consultancy, Advisory Board: Sanofi; Advisory/Consultancy, Advisory Board: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Advisory Board, speaker fees, assistance with travel: AstraZeneca. N. Clarke: Advisory/Consultancy, Consultation and advisory fees: Janssen; Advisory/Consultancy, Consultation/ Lecture fees: Astellas; Advisory/Consultancy, Consultation / Advisory fees: Bayer. G. Attard: Speaker Bureau/Expert testimony, Speakers' bureaus: Sanofi Aventis. D. Dearnaley: Research grant/Funding (institution), C46/A3976, C46/A10588 and C33589/A19727. : Cancer Research UK; Research grant/Funding (self), Consultant and Advisory Board Honoraria: Takeda; Research grant/Funding (self), Consultant and Advisory Board Honoraria: Amgen; Research grant/Funding (self), Consultant and Advisory Board Honoraria: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses, Advisory Board, Travel, Accommodation: Sandoz; Advisory/Consultancy, Travel/Accommodation/Expenses, Financial support for trial recruitment, Advisory Board, Speakers Bureau, Travel and Accommodation: Janssen. S. Gillessen: Honoraria (institution), Honorarium payments to hospital: Bayer; Honoraria (institution), Honorarium payments to hospital: Curevac; Honoraria (self), Honoraria (institution), Honorarium payments to hospital: Janssen; Honoraria (institution), Honorarium payments to hospital: Astellas; Honoraria (self), Honoraria (institution), Honorarium payments to hospital: Orion; Honoraria (institution), Honorarium payments to hospital: Max/Vax SA; Honoraria (institution), Honorarium payments to hospital: Ferring; Honoraria (institution), Honorarium payments to hospital: Roche; Honoraria (institution), Honorarium payments to hospital: Innocrin Pharmaceuticals; Honoraria (self), Honorarium payments to hospital: Sanofi; Honoraria (institution), Honorarium payments to hospital: Novartis; Non-remunerated activity/ies, Uncompensated advisory role: Nectar Therapeutics; Non-remunerated activity/ies, Uncompensated advisory role: ProteoMedix; Honoraria (institution), Honorarium payments to hospital: Cell Search; Honoraria (institution), Honorarium payments to hospital: Clovis; Honoraria (institution), Honorarium payments to hospital: Bristol-Myers Squibb; Honoraria (institution), Honorarium payments to hospital: MSD Merck Sharp & Dome. A. Birtle: Honoraria (self), Advisory/Consultancy, Advisory Board Honoraria: Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Speaker Fee + Advisory Board Honoraria: Sanofi; Honoraria (self), Advisory/Consultancy, Advisory Board Honoraria: Janssen; Advisory/Consultancy, Advisory Board Honoraria: Bayer; Advisory/Consultancy, Advisory Board Honoraria: Astra Zeneca. S. Chowdhury: Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Honoraria, Speakers fee, Travel Grant: Janssen. Z. Malik: Advisory/Consultancy, Advisory boards: Sanofi; Advisory/Consultancy, Advisory boards: Janssen; Advisory/Consultancy, Advisory boards: Pfizer; Travel/Accommodation/Expenses, Assisted travel to Congress: Bayer. J. O'Sullivan: Advisory/Consultancy, Speaker Bureau/Expert testimony, Ad boards + Speakers fees: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Ad boards + Speakers fees: Atellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Ad boards + Speakers fees: Bayer. C. Pezaro: Honoraria (self), Honoraria (institution): Astellas; Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Janssen; Honoraria (self), Honoraria (institution): Mundipharma; Honoraria (self), Honoraria (institution): Pfizer; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Janssen. D. Sheehan: Travel/Accommodation/Expenses, Sponsorship for meeting attendance: Astellas; Travel/Accommodation/Expenses, Sponsorship for meeting attendance: Ipsen. J. Tanguay: Travel/Accommodation/Expenses, Conference attendance: Roche; Travel/Accommodation/Expenses, Conference attendance: Janssen; Advisory/Consultancy, Advisory board: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses, Advisory board & conference attendance: Bayer; Advisory/Consultancy, Advisory board: AstraZeneca. M.K. Parmar: Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Astellas; Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Clovis; Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Novartis; Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Pfizer; Research grant/Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Sanofi. M.R. Sydes: Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Clovis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Sanofi-Aventis; Honoraria (self): Eli-Lilly. All other authors have declared no conflicts of interest.
Invited Discussant 611O
- Maria De Santis (Berlin, Germany)
Q&A and live discussion
- Silke Gillessen (Bellinzona, Switzerland)