Abstract 832P
Background
mUM has poor prognosis. Unlike cutaneous melanoma, PD1+IPI shows modest efficacy. In phase 2 trials median progression-free survival (mPFS) ranges between 3-5.5 mo. Tebe, a soluble T-cell receptor and CD3-directed bispecific fusion protein, resulted in prolonged overall survival (OS) (21.7 mo) in a phase 3 study, but median duration of response (mDOR) was short and PFS benefit modest. The optimal sequence of tebe and PD1+IPI is unknown.
Methods
Retrospective study from 12 cancer centers investigating the efficacy of the sequence of tebe followed by PD1+IPI (Group 1) to the converse sequence (Group 2). Primary endpoints: overall response rate (ORR), disease control rate (DCR) and PFS. Secondary endpoint: OS. Kaplan Meier method was used for time to event analyses. Log-rank test was used for differences between groups.
Results
59 pts were included (26 in Group 1; 33 in Group 2); median age 54 yrs (16-80); 32 (54%) female; median f/u 26 mo (17-38). Differences of baseline characteristics between groups included hepatic + extra-hepatic (46% v 36%) mets, ECOG PS ≥1 (15% v 21%), LDH >ULN at baseline (42% v 24%) and time between tebe and PD1+IPI (and vice versa) (21 v 85 days). Total mPFS was similar in Group 1 and Group 2 (Table). Total mOS was numerically higher in group 2 (55.6 v 37.6 mo). ORR for PD1+IPI was 15% v 6%. Stable disease (SD) was more common in tebe (38% v 39%) than PD1+IPI (12% v 30%). DCR for tebe was similar in Group 1 and 2 (46% v 45%). 73% in Group 1 and 36% in Group 2 were treated beyond tebe PD. Gr 3/4 toxicities occurred in 19% v 30% for IPI+PD1 and 42% v 9% for tebe. Discontinuation due to toxicity was common in PD1+IPI (27% v 39%). PD was common reason for discontinuation in tebe (85% v 48%). Table: 832P
| Group 1 Tebe followed by PD1+IPI (n=26) | Group 2 PD1+IPI followed by Tebe (n=33) | ||||||
| Total (both therapies) | Tebe | PD1+IPI | Total (both therapies) | Tebe | PD1+IPI | ||
| Treatment Duration (med, range) | - | 7 mo (0-31) | 2 mo (0-36) | - | 6 mo (1-29) | 2 mo (0-27) | |
| ORR | - | 2/26 (8%) | 4/26 (15%) | - | 2/33 (6%) | 2/33 (6%) | |
| DCR | - | 12/26 (46%) | 7/26 (27%) | - | 15/33 (45%) | 12/33 (36%) | |
| PFS | mPFS mo (med, 95% CI) | 28.4 (13.4-NR) | 3.7 (2.8-10.1) | 2.9 (2.4-NR) | 20.7 (17.1-NR) | 5.6 (4.7-10.8) | 5.4 (2.7-9.3) |
| OS | 1 yr OS (95% CI) | 87% (74-100) | - | - | 87% (76-100) | - | - |
| 2 yr OS (95% CI) | 57% (39-83) | - | - | 75% (58-96) | - | - | |
| 3 yr OS (95% CI) | 57% (39-83) | - | - | 62% (40-96) | - | - | |
| mOS mo (med, 95% CI) | 37.6 (22.4-NR) | - | - | 55.6 (32.6-NR) | - | - |
Conclusions
Tebe was active prior to or after PD1+IPI (DCR 46% v 45%). PD1+IPI showed similar efficacy in Group 1 and Group 2. After tebe failure, PD+IPI was active. Data collection is ongoing and additional information will be presented.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J.C. Hassel: Financial Interests, Personal, Invited Speaker: BMS, Novartis, sanofi, MSD, Sunpharma, Almirall, Roche, Amgen, GSK, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, Pierre Fabre, Sunpharma, GSK; Financial Interests, Institutional, Advisory Board: Novartis, BMS, Immunocore, Nektar, Philogen; Financial Interests, Institutional, Research Grant: BMS, Sunpharma; Financial Interests, Institutional, Invited Speaker: Philogen, BMS, Genentech, Immunocore, Immunocore, 4SC, Novartis, BioNTech, Idera, Iovance, Nektar, Pierre Fabre, Regeneraon, Sanofi; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. M. Orloff: Financial Interests, Personal, Advisory Role: Immunocore; Financial Interests, Personal, Advisory Board: Trisalus. E. Kapiteijn: Financial Interests, Institutional, Advisory Board: BMS, Novartis, Pierre Fabre, Merck, Delcath, Bayer; Financial Interests, Institutional, Invited Speaker: BMS. D.B. Johnson: Financial Interests, Institutional, Advisory Board: Array Biopharma, Bristol Myers Squibb, Catalyst Biopharma, Iovance Biotherapeutics, Janssen, Merck, Novartis. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L. R.D. Carvajal: Financial Interests, Institutional, Advisory Board: BMS, Merck, Novartis, Pfizer. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaviVAX SA, touchIME, T3 Pharma, Pfizer. All other authors have declared no conflicts of interest.