Abstract 637P
Background
Metacure is a randomized phase 2 platform trial evaluating if a MM strategy can eliminate disease (dz) in patients (pts) with hormone-sensitive HRL or LVM prostate cancer that is incurable by a single modality. During 10 cycles (C) of systemic tx, pts undergo stereotactic radiotherapy (SBRT) at C4 for bone metastases, if applicable, RP and pelvic +/- retroperitoneal lymph node dissection at C7, and adjuvant RT between C7 and C9 based on surgical pathology.
Methods
Pts were enrolled in cohorts A (HRL), B1 (de novo LVM) or B2 (post-RP with PET-detected M1). Primary endpoints were pathologic complete response and minimal residual dz. Secondary endpoints of PSA0 and T recovery rates are reported.
Results
76 pts were enrolled (33 in both Cohorts A and B1, 10 in B2) with a median age of 64. Tx arms are analyzed in combination because no significant differences in outcomes were observed. 58 pts (76%) had Gleason ≥ 8 dz. 35 (81%) pts in cohorts B1 and B2 received SBRT and 12 (18%) pts in cohorts A and B1 received adjuvant RT. Median follow-up after completion of systemic tx was 11.9 (cohort A), 5.3 (cohort B1) and 8.1 (cohort B2) months. All pts achieved castrate T by C2. Median time to T recovery from the end of systemic tx was 4.9 months and 51% of pts recovered T by 6 months post-tx. 3 pts in cohort A discontinued systemic tx due to toxicity and 3 in cohort B1 discontinued due to progression. Table: 637P
| Cohort | PSA0 Pre-SBRT C3 | PSA0 Post-SBRT C5 | PSA0 Pre-RP C7 | PSA0 Post-RP C8 | PSA0 at 12 mo | T Recovery at 12 mo | PSA0 and T Recovery at 18 mo |
| A (N=33) | - | - | 30/33 (91) | 30/33 (91) | 29/32 (91) | 10/32 (31) | 21/30 (70) |
| B1 (N=33) | 19/33 (58) | 29/33 (88) | 27/32 (82) | 28/31 (90) | 24/27 (89) | 4/27 (15) | 4/12 (33) |
| B2 (N=10) | 7/9 (78) | 7/8 (88) | - | - | 7/7 (100) | 3/7 (43) | 4/4 (100) |
Units: N (%)
Conclusions
MM trials are feasible and provide rapid readout of efficacy that can accelerate drug development and support definitive phase III trial designs. T recovered quickly in all pts. Clinical trial: NCT03436654. PCCTC-managed; Janssen-funded; Grant funding by PCF and DOD.
Clinical trial identification
NCT03436654.
Editorial acknowledgement
Legal entity responsible for the study
Memorial Sloan Kettering Cancer Center.
Funding
Janssen Pharmaceuticals.
Disclosure
M.Y. Teo: Financial Interests, Personal and Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Funding: Clovis Oncology; Financial Interests, Personal and Institutional, Funding: Pharmacyclics. S. McBride: Financial Interests, Personal and Institutional, Funding: Genentech; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: AstraZeneca. J.A. Eastham: Financial Interests, Personal, Ownership Interest: 3D Biopsy. A. Goh: Financial Interests, Personal, Advisory Role: Medtronic. R. Szmulewitz: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Corcept Therapeutics; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: Patent licensed by University of Chicago of which I am co-inventor to Corcept Therapeutics for combination AR/GR inhibition in prostate cancer; Financial Interests, Personal, Invited Speaker, Honoraria: Astellas Pharma; Financial Interests, Personal and Institutional, Funding: Abbvie; Financial Interests, Personal and Institutional, Funding: Astellas Pharma; Financial Interests, Personal and Institutional, Funding: Incyte; Financial Interests, Personal and Institutional, Funding: Macrogenics; Financial Interests, Personal and Institutional, Funding: Janssen Oncology. A.K. Morgans: Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications; Financial Interests, Personal, Advisory Role: Myovant Sciences; Financial Interests, Personal, Advisory Role: Blue Earth Diagnostics; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi; Financial Interests, Personal, Invited Speaker: Genentech; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Astellas Scientific and Medical Affairs Inc; Financial Interests, Personal, Invited Speaker: Astellas Pharma; Financial Interests, Personal, Invited Speaker: Janssen Oncology; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Clovis Oncology; Financial Interests, Personal, Invited Speaker: Myovant Sciences; Financial Interests, Personal, Invited Speaker: Advanced Accelerator Applications; Financial Interests, Personal, Invited Speaker: Exelixis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal and Institutional, Funding: Bayer; Financial Interests, Personal and Institutional, Funding: Seattle Genetics/Astellas; Financial Interests, Personal and Institutional, Funding: Genentech; Financial Interests, Personal and Institutional, Funding: AstraZeneca; Financial Interests, Personal and Institutional, Funding: Astellas Scientific and Medical Affairs Inc; Financial Interests, Personal, Advisory Role: Myriad Genetics. S. Gupta: Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Janssen Oncology; Financial Interests, Personal, Speaker’s Bureau: Exelixis; Financial Interests, Personal, Other, Stock and Other Ownership Interests: Nektar; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Exelixis; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Seattle Genetics; Financial Interests, Personal and Institutional, Funding: Merck; Financial Interests, Personal and Institutional, Funding: Pfizer; Financial Interests, Personal and Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Funding: Seattle Genetics. E.A. Klein: Financial Interests, Personal, Advisory Role: GRAIL. P. Nguyen: Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Boston Scientific; Financial Interests, Personal, Advisory Role: COTA; Financial Interests, Personal, Advisory Role: Myovant Sciences; Financial Interests, Personal, Advisory Role: Bayer HealthCare Pharmaceuticals, Inc.; Financial Interests, Personal, Funding: Astellas Pharma; Financial Interests, Personal, Funding: Janssen; Financial Interests, Personal, Funding: Bayer HealthCare Pharmaceuticals, Inc. A.S. Kibel: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Advantagene; Financial Interests, Personal, Invited Speaker: profound; Financial Interests, Personal, Invited Speaker: InSightec; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: GE Healthcare; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Role: Profound Medical; Financial Interests, Personal, Advisory Role: InSightec; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Advantagene; Financial Interests, Personal, Advisory Role: Bayer HealthCare Pharmaceuticals, Inc. A. Wagner: Financial Interests, Personal, Advisory Role: PatientApps; Financial Interests, Personal, Stocks/Shares, equity holder: PatientApps. S.E. Eggener: Financial Interests, Personal, Advisory Role: Francis Medical; Financial Interests, Personal, Advisory Role: InSightec; Financial Interests, Personal, Advisory Role: Profound Medical; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen Biotech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: InSightec; Financial Interests, Personal, Other, Uncompensated Relationships: Steba Biotech. S.L. Liauw: Financial Interests, Personal, Stocks/Shares: ARKG. M.E. Taplin: Financial Interests, Personal, Advisory Role: Janssen-Ortho; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Guidepoint Global; Financial Interests, Personal, Advisory Role: Best Doctors, Inc; Financial Interests, Personal, Advisory Role: UpToDate; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Research to Practice; Financial Interests, Personal, Advisory Role: Myovant Sciences; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Arcus Ventures; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Medivation; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Tokai Pharmaceuticals; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Incyte; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Clovis Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bayer; Financial Interests, Personal, Invited Speaker: Janssen-Ortho; Financial Interests, Personal, Invited Speaker: Clovis Oncology; Financial Interests, Personal, Invited Speaker: Astellas Pharma; Financial Interests, Personal, Invited Speaker: Incyte; Financial Interests, Personal, Invited Speaker: UpToDate; Financial Interests, Personal, Invited Speaker: Research to Practice; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Progenics; Financial Interests, Personal, Invited Speaker: Guidepoint Global; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: Myovant Sciences; Financial Interests, Personal, Invited Speaker: Roivant; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Abbvie; Financial Interests, Personal, Invited Speaker: Arcus Biosciences; Financial Interests, Personal, Invited Speaker: Constellation Pharmaceuticals; Financial Interests, Personal and Institutional, Funding: Janssen-Ortho; Financial Interests, Personal and Institutional, Funding: Medivation; Financial Interests, Personal and Institutional, Funding: Bayer; Financial Interests, Personal and Institutional, Funding: Pfizer. H. Scher: Financial Interests, Personal, Invited Speaker, compensated Board of Directors Member: Asterias Biotherapeutics; Financial Interests, Personal, Advisory Role, compensated consultant/advisor: Ambry Genetics Corp; Financial Interests, Personal, Advisory Role, compensated consultant/advisor: Konica Minolta Inc; Financial Interests, Personal, Advisory Role, compensated consultant/advisor: Bayer; Financial Interests, Personal, Advisory Role, compensated consultant/advisor: Pfizer Inc; Financial Interests, Personal, Advisory Role, compensated consultant/advisor: Sun Pharmaceuticals; Financial Interests, Personal, Advisory Role, compensated consultant/advisor: WCG Oncology; Financial Interests, Personal, Advisory Role, uncompensated consultant/advisory: Amgen; Financial Interests, Personal, Advisory Role, uncompensated consultant/advisory: ESSA Pharma Inc; Financial Interests, Personal, Advisory Role, uncompensated consultant/advisory: Janssen Research & Development, LLC; Financial Interests, Personal, Advisory Role, uncompensated consultant/advisory: Janssen Biotech, Inc; Financial Interests, Personal, Advisory Role, uncompensated consultant/advisory: Sanofi Aventis; Financial Interests, Personal and Institutional, Funding: Epic Sciences; Financial Interests, Personal and Institutional, Funding: Illumina, Inc; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Personal and Institutional, Funding: Menarini Silicon Biosystems; Financial Interests, Personal and Institutional, Funding: Prostate Cancer Foundation; Financial Interests, Personal and Institutional, Funding: ThermoFisher; Financial Interests, Personal, Proprietary Information, Intellectual Property Rights: BioNTech; Financial Interests, Personal, Proprietary Information, Intellectual Property Rights: Elucida Oncology; Financial Interests, Personal, Proprietary Information, Intellectual Property Rights: MaBVAX; Financial Interests, Personal, Proprietary Information, Intellectual Property Rights: Y-mAbs Therapeutics, Inc; Financial Interests, Personal, Other, non-financial support: Amgen; Financial Interests, Personal, Other, non-financial support: Asterias Biotherapeutics; Financial Interests, Personal, Other, non-financial support: Bayer; Financial Interests, Personal, Other, non-financial support: ESSA Pharma Inc; Financial Interests, Personal, Other, non-financial support: Menarini Silicon Biosystems; Financial Interests, Personal, Other, non-financial support: Phosplatin; Financial Interests, Personal, Other, non-financial support: Pfizer Inc; Financial Interests, Personal, Other, non-financial support: Prostate Cancer Foundation; Financial Interests, Personal, Other, non-financial support: WCG Oncology. All other authors have declared no conflicts of interest.