Rogel Cancer Center, University of Michigan, Ann Arbor, MI;
Oxana V. Crysler , Mark Yarchoan , Junji Furuse , Peter R. Galle , Wattana Sukeepaisarnjaroen , Nguyen Tien Thinh , Gianluca Masi , Ho Yeong Lim , Maria Varela , Charu Gupta , Mallory Makowsky , Alejandra Negro , Ghassan K. Abou-Alfa
Background: ADAs to immune checkpoint inhibitors may decrease antitumor activity in HCC. Reported rates of treatment-emergent ADAs (TE-ADAs) vary from 1.5% for pembrolizumab and 8.6% for nivolumab to 54.1% for atezolizumab across indications (Enrico et al. Clin Cancer Res 2020). In the global, Phase 3 HIMALAYA study (NCT03298451) in uHCC, the STRIDE regimen (Single T Regular Interval D) significantly improved overall survival vs sorafenib (S); D monotherapy was noninferior to S (Abou-Alfa et al. NEJM Evid 2022). Here, we analyzed ADAs to T and D in HIMALAYA. Methods: Prespecified secondary analyses assessed the presence of ADAs to D and T before the first study dose (baseline), once during treatment and once after treatment discontinuation. For participants (pts) who were ADA-positive at any visit (ADA+), presence of neutralizing antibodies (nAbs) was also assessed. TE-ADA+ was defined as pts with a positive post-baseline sample only or pts with an ADA titer that increased ≥4-fold following treatment. ADA negative (ADA-) was defined as pts with no positive sample at any visit, at baseline or post-baseline. Objective response rate (ORR; RECIST v1.1, inc. unconfirmed), overall survival (OS) and treatment-related adverse events (TRAEs) were evaluated in ADA subgroups. Results: The frequency of ADAs to D was similar in the STRIDE (T+D) and D arms: 8.2% (24/294) and 7.1% (20/282) of pts, respectively, were ADA+ to D; 3.1% (9/294) and 2.8% (8/282) of pts, respectively, were TE-ADA+ to D; and 1.7% (5/294) and 0.7% (2/282) of pts, respectively, had nAbs to D. In the STRIDE arm, 15.9% (29/182) of pts were ADA+ to T, 11.0% (20/182) of pts were TE-ADA+ to T, and 4.4% (8/182) of pts had nAbs to T. Although the number of pts was small, in the STRIDE arm, ORR was 11.1% (1/9) in pts TE-ADA+ to D, 35.0% (7/20) in pts TE-ADA+ to T and 23.9% (94/393) in the full analysis set (FAS). In the D arm, ORR was 25.0% (2/8) in pts TE-ADA+ to D and 18.5% (72/389) in the FAS. OS for pts TE-ADA+/nAb+ to D or T in the D and STRIDE arms was consistent with the FAS. In both arms, TRAE and Grade 3/4 TRAE rates were not increased in the ADA+ vs ADA- groups (Table) and were generally consistent with the overall population. Conclusions: In HIMALAYA, the rates of TE-ADAs and nAbs to D and T were low (≤11%). The presence of ADAs did not appear to impact clinical efficacy or safety of STRIDE or D monotherapy in the small number of ADA+ pts. These results support a low risk of ADAs for STRIDE or D in uHCC. Clinical trial information: NCT03298451.
ADA to | D | D | D | D | T | T |
---|---|---|---|---|---|---|
ADA status | + | - | + | - | + | - |
Treatment arm | STRIDE | STRIDE | D | D | STRIDE | STRIDE |
n | 24 | 270 | 20 | 262 | 29 | 153 |
TRAEs, n (%) | 17 (70.8) | 213 (78.9) | 9 (45.0) | 148 (56.5) | 23 (79.3) | 120 (78.4) |
Grade 3/4 TRAEs, n (%) | 5 (20.8) | 66 (24.4) | 2 (10.0) | 32 (12.2) | 7 (24.1) | 37 (24.2) |
Serious TRAEs, n (%) | 1 (4.2) | 43 (15.9) | 0 | 17 (6.5) | 7 (24.1) | 25 (16.3) |
TRAEs leading to discontinuation, n (%) | 1 (4.2) | 16 (5.9) | 0 | 6 (2.3) | 3 (10.3) | 11 (7.2) |
Infusion reaction AEs, n (%) | 0 | 16 (5.9) | 0 | 5 (1.9) | 2 (6.9) | 10 (6.5) |
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Abstract Disclosures
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