Abstract 5180
Background
Ra-223 demonstrated improvements in overall survival (OS) and time to symptomatic skeletal events (SSEs) in patients (pts) with mCRPC and bone metastases in the ALSYMPCA study (Parker C et al. N Engl J Med 2013; 369:213–223). The current study investigated antitumor activity of Ra-223 alone or in combination with abiraterone (abi) or enzalutamide (enza).
Methods
In this multicenter, open-label phase 2a study, pts with mCRPC and bone-only metastases were randomized (1:1:1) to: six injections of Ra-223 (55 kBq/kg, q4w), Ra-223+abi (1000 mg qd + prednisone 5 mg bid), or Ra-223+enza (160 mg qd). The primary endpoint was bone scan lesion area response rate (BSLA RR) at Week 24 based on the quantified technetium-99 bone scan. BSLA RR, defined as > 30% decrease from baseline (BL), was evaluated centrally. The hypothesis of a BSLA RR ≥ 5% at Week 24 was tested in each arm separately. No cross-arm comparisons were planned. Secondary endpoints are shown in the table.
Results
68 pts were randomized; 63 received treatment. The most common reason for treatment discontinuation was disease progression (50.0%). Approximately 36.5% of pts used bone health agents (BHAs) at BL. The primary endpoint of BSLA RR at Week 24 was 57.9%, 50.0%, and 22.2% for the Ra-223+abi, Ra-223+enza, and Ra-223 groups, respectively. Median SSE-free survival (SSE-FS) was not reached, 19.91, and 11.93 months and median OS was 37.55, 29.86, and 35.81 months, for the Ra-223+abi, Ra-223+enza, and Ra-223 groups, respectively. Fracture rates were lower in pts with vs without BL BHAs; 3/23 (13.0%) vs 10/40 (25.0%), respectively. 17, 18, and 8 pts receiving Ra-223+abi, Ra-223+enza, and Ra-223 experienced related treatment-emergent adverse events, respectively.Table:
870P
Ra-223 + abi (n = 22) | Ra-223 + enza (n = 22) | Ra-223 (n = 19) | |
---|---|---|---|
BL, median (min, max) | |||
Age, years | 68 (56, 86) | 73 (56, 86) | 71 (54, 91) |
PSA, µg/L | 19.0 (0.90, 1500.0) | 19.3 (1.2, 805.9) | 23.1 (0.05, 617.0) |
ECOG 0/1, n (%) | 13 (59.1)/9 (40.9) | 11 (50.0)/11 (50) | 10 (52.6)/9 (47.4) |
Time since PC diagnosis, months | 51.4 (2.6, 196.0) | 48.3 (5.1, 198.0) | 38.34 (6.6, 252.9) |
Extent of disease, n (%) <6 metastases 6–20 metastases >20 lesions Superscan | 6 (27.3) 10 (45.5) 5 (22.7) 0 | 6 (27.3) 12 (54.5) 4 (18.2) 0 | 9 (47.4) 7 (36.8) 2 (10.5) 1 (5.3) |
Prior therapies, n (%)* Sipuleucel-t Docetaxel Cabazitaxel | 6 (25.0) 3 (12.5) | 3 (13.6) 5 (22.7) 1 (4.5) | 5 (22.7) 4 (18.2) |
Efficacy | |||
BSLA RR, % (80% CI)** | 57.9 (40.8–73.7); p < 0.0001† | 50.0 (31.8–68.2); p < 0.0001† | 22.2 (10.1–39.6); p = 0.0109† |
SSE, n (%) | 7 (31.8) | 7 (31.8) | 6 (31.6) |
Median SSE-FS, months (80% CI) | NE (17.3–NE) | 19.9 (12.2–28.1) | 11.9 (10.1–24.6) |
Median OS, months (80% CI) | 37.6 (35.9–NE) | 29.9 (26.6–NE) | 35.8 (21.3–41.4) |
Safety, n | |||
TEAEs | 22 | 22 | 18 |
Treatment-related TEAEs | 17 | 18 | 8 |
Fractures (+BL BHA)§ | 0 | 2 | 1 |
Fractures (-BL BHA)¶ | 4 | 5 | 1 |
Ra-223+abi (n = 24); Ra-223+enza (n = 22); Ra-223 (n = 22).
**Ra-223+abi (n = 19); Ra-223+enza (n = 16); Ra-223 (n = 18).
†Test of the null hypothesis of BSLA RR at Week 24 ≤5% using an exact single-arm binomial test in each treatment group with one-sided alpha=0.10.
§Ra-223+abi (n = 7); Ra-223+enza (n = 8); Ra-223 (n = 8).
¶Ra-223+abi (n = 15); Ra-223+enza (n = 14); Ra-223 (n = 11).
Conclusions
The primary endpoint of BSLA response was met in each treatment arm. Overall, OS does not appear to correlate with BSLA RR in this small study population.
Clinical trial identification
NCT02034552.
Editorial acknowledgement
Jenny Feehan of OPEN Health Medical Communications (London, UK), with financial support from Bayer.
Legal entity responsible for the study
Bayer HealthCare Pharmaceuticals.
Funding
Bayer HealthCare Pharmaceuticals.
Disclosure
D.P. Petrylak: Advisory / Consultancy, Research grant / Funding (institution): Ada Cap (Advanced Accelerator Applications); Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy: Exelixis; Research grant / Funding (institution): Endocyte; Advisory / Consultancy: Incyte; Research grant / Funding (institution): Innocrin; Advisory / Consultancy: Incyte; Research grant / Funding (institution): Genentech; Advisory / Consultancy: Janssen, Pharmacyclics, Urogen; Research grant / Funding (institution): MedImmune, Merck; Research grant / Funding (institution): Novartis, Progenics, Sanofi Aventis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer, Roche Laboratories, Seattle Genetics; Shareholder / Stockholder / Stock options: Bellicum, Tyme. U.N. Vaishampayan: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer Inc. C.S. Higano: Advisory / Consultancy, Research Grant / Funding (Institution): Aptevo; Advisory / Consultancy: Asana; Advisory / Consultancy, Research Grant / Funding (Institution): Astellas; Advisory / Consultancy, Research Grant / Funding (Institution): AstraZeneca; Advisory / Consultancy, Research Grant / Funding (Institution), Travel/Accommodation/Expenses: Bayer; Advisory / Consultancy, Travel/Accommodation/Expenses: Blue Earth Diagnostics; Advisory / Consultancy: Churchill Pharma; Advisory / Consultancy, Travel/Accommodation/Expenses: Clovis Oncology; Advisory / Consultancy, Research Grant/Funding (Institution): Dendreon; Advisory / Consultancy: Endocyte; Advisory / Consultancy, Travel/Accommodation/Expenses: Ferring; Advisory / Consultancy, Travel/Accommodation/Expenses: Hinova; Advisory / Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory / Consultancy, Travel/Accommodation/Expenses: Myriad; Advisory / Consultancy, Travel/Accommodation/Expenses: Orion Corporation; Advisory / Consultancy, Research Grant / Funding (Institution), Travel/Accommodation/Expenses: Pfizer, Research Grant / Funding (Institution), Travel/Accommodation/Expenses: Genentech, Research Grant / Funding (Institution): Hoffmann-La Roche Research Grant / Funding (Institution): Medivation, Research Grant / Funding (Institution): Sanofi; Research Grant / Funding (Institution): Aragon Pharma. C. Albany: Speaker Bureau / Expert Testimony: Sanofi. N. Dawson: Speaker Bureau / Expert Testimony: Astellas/ Pfizer, Speaker Bureau / Expert Testimony: Janssen. B. Mehlhaff: Honoraria (self), Advisory / Consultancy, Research Grant / Funding (Institution), Travel/ Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Research Grant / Funding (Institution), Travel/ Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research Grant / Funding (Institution), Travel/ Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Research Grant / Funding (Institution), Travel/ Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel/ Accommodation / Expenses: Amgen. D. Quinn: Research Grant/Funding (Institution): Seattle Genetics. Research Grant/Funding (Institution), Advisory / Consultancy, Travel/Accommodations/ Expenses: MSD. Research Grant/Funding (Institution), Advisory / Consultancy: Novartis. Advisory/Consultancy: Astellas. Advisory/Consultancy, Travel / Accommodations/ Expenses: AstraZeneca. Advisory/Consultancy: Bayer. Advisory/Consultancy, Travel / Accommodations/ Expenses: BMS. Advisory/Consultancy: Dendreon. Advisory/Consultancy: Exelixis. Advisory/Consultancy, Travel / Accommodations/ Expenses: Roche. Advisory/Consultancy: Janssen. Advisory/Consultancy, Travel / Accommodations/ Expenses: Pfizer. Advisory/Consultancy: Sanofi.V.J. Wagner: Full / Part-time employment: Bayer Pharmaceuticals. J. Shen: Full / Part-time employment: Bayer Pharmaceuticals. L. Trandafir: Full / Part-time employment: Bayer Pharmaceuticals. O. Sartor: Advisory/Consultancy: Advanced Accelerator Applications (AAA); Advisory/Consultancy: Astellas; Advisory/Consultancy, Research Grant/Funding (Institution): AstraZeneca; Advisory/Consultancy, Research Grant/Funding (Institution): Bayer; Advisory/Consultancy: Blue Earth; Advisory/Consultancy: Board of Scientific Counselors; Advisory/Consultancy: Diagnostics, Inc; Advisory/Consultancy, Research Grant/Funding (Institution): Constellation; Advisory/Consultancy, Research Grant/Funding (Institution): Dendreon; Advisory/Consultancy: EMD Serono; Advisory/Consultancy, Research Grant/Funding (Institution): Endocyte; Advisory/Consultancy: Hinova; Advisory/Consultancy, Research Grant/Funding (Institution): Johnson & Johnson; Advisory/Consultancy: Myovant; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research Grant/Funding (Institution): Progenics; Advisory/Consultancy, Research Grant/Funding (Institution), Speaker Bureau/Expert Testimony: Sanofi; Research Grant/Funding (Institution): Innocrin; Research Grant/Funding (Institution): Invitae; Research Grant/Funding (Institution): Merck; Research Grant/Funding (Institution): SOTIO; Leadership Role: Co-Chairman of GU Committee. All other authors have declared no conflicts of interest.
Resources from the same session
1802 - Evaluation of the anti-tumor efficacy and immune effects of N-809, a novel IL-15 superagonist/anti-PD-L1 bispecific agent
Presenter: Kristin Hicks
Session: Poster Display session 3
Resources:
Abstract
3190 - GI101, a novel triple-targeting bispecific CD80-IgG4-IL2variant fusion protein, elicits synergistic anti-tumor effects in preclinical models
Presenter: Jae Chan Park
Session: Poster Display session 3
Resources:
Abstract
4062 - Phase 1b, open-label, dose-escalation study of M9241 (NHS-IL12) plus avelumab in patients (pts) with advanced solid tumors
Presenter: Julius Strauss
Session: Poster Display session 3
Resources:
Abstract
5777 - THOR-707, a novel not-alpha IL-2, promotes all key immune system anti-tumoral actions of IL-2 without eliciting vascular leak syndrome (VLS)
Presenter: Marcos Milla
Session: Poster Display session 3
Resources:
Abstract
5047 - A phase I clinical trial of malignant pleural mesothelioma treated with locally delivered autologous anti-FAP-targeted CAR T-cells
Presenter: Alessandra Curioni
Session: Poster Display session 3
Resources:
Abstract
1679 - HPV16 E6-specific TCR-T armored with checkpoint blockade in the treatment of cervical cancer
Presenter: Paul Bryson
Session: Poster Display session 3
Resources:
Abstract
1133 - the Mutant Neoantigen Specific T Cell Is a Personalized Immunotherapy in Refractory Solid Tumor
Presenter: Qi Song
Session: Poster Display session 3
Resources:
Abstract
3338 - NY-ESO-1 and LAGE1A –an emerging target for cell therapies in solid tumours
Presenter: Ioanna Eleftheriadou
Session: Poster Display session 3
Resources:
Abstract
3089 - Targeting myeloid-derived suppressor cells and T cells: combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model
Presenter: Mikael Sodergren
Session: Poster Display session 3
Resources:
Abstract
5991 - Master Checkpoint Cbl-b Inhibition: Anti-tumor Efficacy in a Murine Colorectal Cancer Model Following siRNA-based Cell Therapy
Presenter: Kathrin Thell
Session: Poster Display session 3
Resources:
Abstract