1027MO - ALKS 4230 monotherapy and in combination with pembrolizumab (pembro) in patients (pts) with refractory solid tumours (ARTISTRY-1)

Background

ALKS 4230 is a fusion protein of circularly permuted interleukin-2 (IL-2) & IL-2Rα designed to selectively bind to the intermediate-affinity IL-2 receptor. ALKS 4230 is being investigated as monotherapy & in combination with pembro in pts with solid tumors. We report extended follow-up from combination therapy and new ALKS 4230 monotherapy data.

Methods

ARTISTRY-1 (NCT02799095) is an ongoing 3-part phase I/II study. In Parts A (dose escalation) and B (expansion), ALKS 4230 is administered as IV monotherapy on days 1-5 of 14- or 21-day cycles. In Part C (combination therapy), ALKS 4230 is administered via the same 5-day regimen q21d with pembro on day 1. Outcomes presented include safety, PK/pharmacodynamics, RP2D, and antitumor activity (RECIST v1.1 & iRECIST) from Parts B & C (response data cut: 4/29/2020; all other data: 3/23/2020).

Results

In Part B, 9 pts (5 melanoma, 4 RCC) received 6 μg/kg (RP2D). The most common adverse events (AEs) were grade ≤2 (fevers, chills, hypotension [not requiring vasopressors]). No treatment-related deaths occurred; no AEs led to treatment discontinuation. One pt with metastatic urethral melanoma (which had previously recurred following adjuvant nivolumab) achieved partial response (PR) to 6 μg/kg ALKS 4230 monotherapy with normalization of serum LDH. In Part C, 46 pts (13 tumor types) received ALKS 4230 (3 μg/kg) and pembro. The most common tumor types (≥5 each) were colorectal, ovarian (OC), & sarcoma. Addition of pembro did not alter the PK/pharmacodynamics of ALKS 4230; no new toxicities were observed. Among pts with ≥1 scan, 1 heavily pretreated pt with OC achieved complete response (per RECIST) & continues therapy >12 months; PR was seen in 2 other OC pts (1 pt awaiting confirmatory scan) who received therapy for 7 & 3 months, respectively, both ongoing; iPR was seen in 1 pt with triple-negative breast cancer (on therapy >12 months). All 4 responders were checkpoint inhibitor naive.

Conclusions

ALKS 4230 is a promising novel agent given its tolerability & efficacy profile, which includes single agent activity & durable responses even in a pretreated pt population. Future research of mono & combination therapy with ALKS 4230 is warranted.

Clinical trial identification

NCT02799095.

Editorial acknowledgement

Medical writing and editorial support was provided by Parexel and funded by Alkermes, Inc.

Legal entity responsible for the study

Alkermes, Inc.

Funding

Alkermes, Inc.

Disclosure

U.N. Vaishampayan: Honoraria (self), Advisory/Consultancy: Alkermes; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Merck. V. Velcheti: Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: EMD Serono. C.J. Hoimes: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Astellas; Honoraria (self), Advisory/Consultancy: Foundation Medicine; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Merck; Research grant/Funding (institution): 2bPrecise. A. Spreafico: Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Oncorus; Advisory/Consultancy: Janssen; Research grant/Funding (self): Symphogen; Research grant/Funding (self): AstraZeneca/MedImmune; Research grant/Funding (self): Bayer; Research grant/Funding (self): Surface Oncology; Research grant/Funding (self): Northern Biologics; Research grant/Funding (self): Janssen Oncology/J&J; Research grant/Funding (self): Roche; Research grant/Funding (self): Regeneron; Research grant/Funding (self): Alkermes; Research grant/Funding (self): Array Biopharma. D.F. McDermott: Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Alkermes; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Iovance; Advisory/Consultancy: Eisai; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): X4 Pharma; Leadership role: GU Committee Eastern Cooperative Oncology Group; Leadership role: Renal Cell Carcinoma Task Force, National Cancer Institute; Leadership role: Melanoma Breakthrough Consortium Melanoma Research Foundation; Leadership role: Cancer Immunotherapy Guidelines Kidney Task Force Society for Immunotherapy of Cancer. Q.S-C. Chu: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): BI; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Officer/Board of Directors: Epizyme; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Apollomics; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Debio; Research grant/Funding (institution): Esperas; Research grant/Funding (institution): Exactis; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Spectrum; Research grant/Funding (institution): Takeda and TP Therapeutics; Leadership role: IND Committee and Lung Committee of Canadian Clinical Trials Group; Non-remunerated activity/ies: Canadian Mesothelioma Foundation; Non-remunerated activity/ies: Princess Margaret Cancer Centre; Leadership role: Merck KGaA. L. Gilbert: Full/Part-time employment: Synoes; Research grant/Funding (self): Alkermes. H. Hirte: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Merck; Research grant/Funding (institution): BI; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Immunogen; Research grant/Funding (institution): Immunovac; Research grant/Funding (institution): Alkermes; Leadership role: Canadian Cancer Trials Group (CCTG) - Gynecologic Disease Site Committee; Leadership role: Gynecologic Oncologists of Canada (GOC); Leadership role: Canadian Association of Medical Oncologists (CAMO). K.K. Curtis: Full/Part-time employment: Synoes; Research grant/Funding (self): Alkermes. Y. Du: Full/Part-time employment: Alkermes, Inc. I. Bidollari: Shareholder/Stockholder/Stock options, Full/Part-time employment: Alkermes, Inc.; Shareholder/Stockholder/Stock options, Full/Part-time employment: Teva; Full/Part-time employment: Novartis. L. Sun, E. Putiri, B. Dezube: Shareholder/Stockholder/Stock options, Full/Part-time employment: Alkermes, Inc. H.C. Losey: Shareholder/Stockholder/Stock options, Full/Part-time employment: Alkermes, Inc.; Shareholder/Stockholder/Stock options: BMS. M.S. Ernstoff: Honoraria (self), Advisory/Consultancy, Leadership role, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Alkermes; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): EMD Serono; Advisory/Consultancy: ImmuNext; Advisory/Consultancy: OmniSeq. All other authors have declared no conflicts of interest.