OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients (pts) with immune checkpoint inhibitor (ICI)–resistant advanced melanoma: Phase 1 results of the Agni-01 multicenter study.
Year: 2025
Type: conference-abstract
Abstract: 9517 Background: OBX-115 TIL are engineered to express mbIL15 regulated by the FDA-approved small-molecule drug acetazolamide (ACZ), abrogating the need for toxic high-dose IL2 after TIL infusion. Single-center phase 1 data (NCT05470283) demonstrated differentiated early safety (Amaria ASCO 2024). We report the first data evaluating OBX-115 in pts with advanced melanoma in the multicenter phase 1/2 Agni-01 study (NCT06060613). Methods: This single-arm, open-label study assesses safety, tolerability, and efficacy of the OBX-115 TIL cell therapy regimen in pts with advanced melanoma and NSCLC (Shoushtari AACR 2025). Phase 1 characterizes safety (treatment-emergent adverse events [TEAEs]: AEs ≤30 d after OBX-115 infusion) and tolerability in escalating dose levels of OBX-115 and ACZ to establish a recommended phase 2 dose (RP2D). Phase 2 evaluates efficacy of the regimen at RP2D (RECIST v1.1 per investigator). OBX-115 is manufactured from pt tumor tissue (core needle biopsy or surgical excision) and infused after standard- or low-dose (Cy 750 mg/m 2 /d × 3; Flu 30 mg/m 2 /d × 4) lymphodepletion (LD). No IL2 is administered. Oral ACZ starts day of OBX-115 infusion (QD up to 14 d), and is redosed (QD up to 7 d) every 6 wks after recovery from LD. Results: In phase 1,as of 01 Jan 2025, OBX-115 was successfully manufactured and infused for 11 pts with ICI-resistant advanced melanoma (median study follow-up, 22.3 wks [range, 13.3–52.1]) including 6 treated at RP2D (OBX-115 1–100×10 9 cells, ACZ 500 mg/d). Majority (n = 10) received low-dose LD, including 1 in the outpatient setting. There was no dose-limiting toxicity (DLT), treatment-emergent ICU transfer, or treatment-related mortality (TRM). Eight pts had G≥3 nonhematologic TEAEs (events in > 1 pt: hyponatremia, hypokalemia [n = 2 each]). One pt reported 2 OBX-115–related serious AEs, including 1 CRS event (G2) without IL6 elevation (IL6 < 100 pg/mL). Across dose levels (n = 11), confirmed ORR was 36% (4 PR, 5 SD; DCR 82%). For 6 pts receiving RP2D, ORR was 67% (4 PR, 2 SD; DCR 100%). Conclusions: Early data support clinical benefit (RP2D ORR 67%, DCR 100%) of OBX-115regulatableengineeredTIL cell therapy in the absence of IL2, including with outpatient low-dose LD. The safety profile is highly differentiated, without TRM, ICU transfer, or high-grade CRS. ACZ redosing is well-tolerated and offers an opportunity to deepen responses by inducing re-expression of mbIL15 on engrafted OBX-115 TIL, a unique capability among adoptive cell therapies. These attributes may comprehensively address the unmet need in post-ICI advanced melanoma and other cancers, and data support continued investigation of OBX-115 in the ongoing phase 2 portion of the Agni-01 study. Clinical trial information: NCT06060613 .
Source: Journal of Clinical Oncology
Institutions: University of Louisville, University of Southern California, USC Norris Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center, Angeles Clinic and Research Institute, Allegheny Health Network, Orlando Health, The University of Texas MD Anderson Cancer Center, Stanford Medicine, Stanford University
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410818559