3 Key Takeaways
Plain English Summary- 01Core Finding
In two single-arm trials (completed Phase 1 single-center first-in-human (FIH) and ongoing Phase 1/2 multicenter Agni-01), patients with immune checkpoint inhibitor (ICI)-resistant advanced melanoma received lymphodepletion and varying doses and schedules of amsoki-cel and ACZ.
- 02Study Evidence
Tested in a early human trial + observational cohort study (n = 17) at the Phase I/II stage.
- 03Practical Meaning
In total, 15 patients were treated at RP2D and comprise the Key efficacy (real-world effectiveness in the trial) Set (Agni-01: Phase 1, n = 6; Phase 2, n = 9), of which 10 patients (66.7%; 95% confidence interval 38-88%) achieved objective responses (including two complete responses).
What This Means for You
Serious TEAEs were reported for 10 patients, including eight patients with grade 3 or higher events (non-hematologic, a clinically meaningful level (5/37); hematologic, a clinically meaningful level (5/37)). RP2D was selected based on overall safety and tolerability as well as preliminary anti-tumor activity in Agni-01 Phase 1. In total, 15 patients were treated at RP2D and comprise the Key efficacy (real-world effectiveness in the trial) Set (Agni-01: Phase 1, n = 6; Phase 2, n = 9), of which 10 patients (a clinically meaningful level; a clinically meaningful level confidence interval 38-a clinically meaningful level) achieved objective responses (including two complete responses). Amsoki-cel demonstrated favorable safety and promising early clinical activity in patients with ICI-resistant melanoma. A separate Phase 2 pivotal Agni-01 cohort is ongoing. : NCT05470283 and NCT06060613.
The Discovery
Amsokigene autoleucel (amsoki-cel, OBX-115) is a tumor-infiltrating lymphocyte (TIL) cell therapy engineered to express acetazolamide (ACZ)-regulatable membrane-bound interleukin-15, abrogating the need for interleukin-2. In two single-arm trials (completed Phase 1 single-center first-in-human (FIH) and ongoing Phase 1/2 multicenter Agni-01), patients with immune checkpoint inhibitor (ICI)-resistant advanced melanoma received lymphodepletion and varying doses and schedules of amsoki-cel and ACZ. The primary objective of FIH and Agni-01 Phase 1 was safety, tolerability and recommended Phase 2 dose (RP2D); the primary objective of Agni-01 Phase 2 was objective response rate (ORR) at the RP2D. The first patient treated experienced rapid lymphocyte expansion and vasogenic edema of a previously irradiated brain metastasis, prompting protocol modifications and dose deescalation in FIH, including meaningful reduction in maximum amsoki-cel dose and 75% reduction in ACZ dose. After preliminary demonstration of safety at the lower dose, doses were increased in FIH, and reescalation was initiated in Agni-01. Across studies, 37 patients were treated (FIH, n = 17; Agni-01, n = 20). Post hoc pooled analysis demonstrated no dose-limiting toxicities, ICU care or treatment-related mortality. Most common grade 3 or higher treatment-emergent adverse events (TEAEs) included neutropenia (64.9% (24/37)), leukopenia/lymphopenia (56.8% (21/37) each) and anemia/thrombocytopenia (37.8% (14/37) each).
How It Works, Simply
This pharmacology research focuses on immune response. Researchers evaluated it using an early human trial + Observational cohort study (n = 17) at the Phase I/II stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
In two single-arm trials (completed Phase 1 single-center first-in-human (FIH) and ongoing Phase 1/2 multicenter Agni-01), patients with immune checkpoint inhibitor (ICI)-resistant advanced melanoma received lymphodepletion and varying doses and schedules of amsoki-cel and ACZ.
- 02Study Evidence
Tested in a early human trial + observational cohort study (n = 17) at the Phase I/II stage.
- 03Practical Meaning
In total, 15 patients were treated at RP2D and comprise the Key Efficacy Set (Agni-01: Phase 1, n = 6; Phase 2, n = 9), of which 10 patients (66.7%; 95% confidence interval 38-88%) achieved objective responses (including two complete responses).
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Early human trial + Observational cohort study
Early human trial + Observational cohort study (n = 17) · Phase I/II
Biological Pathway & Modality
Immune response
Intervention: Regulatable membrane-bound IL-15 engineered TIL cell therapy
Experimental Findings & Endpoints
Amsokigene autoleucel (amsoki-cel, OBX-115) is a tumor-infiltrating lymphocyte (TIL) cell therapy engineered to express acetazolamide (ACZ)-regulatable membrane-bound interleukin-15, abrogating the need for interleukin-2.
In two single-arm trials (completed Phase 1 single-center first-in-human (FIH) and ongoing Phase 1/2 multicenter Agni-01), patients with immune checkpoint inhibitor (ICI)-resistant advanced melanoma received lymphodepletion and varying doses and schedules of amsoki-cel and ACZ. The primary objective of FIH and Agni-01 Phase 1 was safety, tolerability and recommended Phase 2 dose (RP2D); the primary objective of Agni-01 Phase 2 was objective response rate (ORR) at the RP2D.
The first patient treated experienced rapid lymphocyte expansion and vasogenic edema of a previously irradiated brain metastasis, prompting protocol modifications and dose deescalation in FIH, including meaningful reduction in maximum amsoki-cel dose and 75% reduction in ACZ dose. After preliminary demonstration of safety at the lower dose, doses were increased in FIH, and reescalation was initiated in Agni-01.
Across studies, 37 patients were treated (FIH, n = 17; Agni-01, n = 20). Post hoc pooled analysis demonstrated no dose-limiting toxicities, ICU care or treatment-related mortality.
Most common grade 3 or higher treatment-emergent adverse events (TEAEs) included neutropenia (64.9% (24/37)), leukopenia/lymphopenia (56.8% (21/37) each) and anemia/thrombocytopenia (37.8% (14/37) each).
Clinical Translation & Practice Context
Serious TEAEs were reported for 10 patients, including eight patients with grade 3 or higher events (non-hematologic, a clinically meaningful level (5/37); hematologic, a clinically meaningful level (5/37)).
RP2D was selected based on overall safety and tolerability as well as preliminary anti-tumor activity in Agni-01 Phase 1. In total, 15 patients were treated at RP2D and comprise the Key Efficacy Set (Agni-01: Phase 1, n = 6; Phase 2, n = 9), of which 10 patients (a clinically meaningful level; a clinically meaningful level confidence interval 38-a clinically meaningful level) achieved objective responses (including two complete responses).
Amsoki-cel demonstrated favorable safety and promising early clinical activity in patients with ICI-resistant melanoma. A separate Phase 2 pivotal Agni-01 cohort is ongoing. : NCT05470283 and NCT06060613.
The Bottom Line · Clinical Pearl
“A separate Phase 2 pivotal Agni-01 cohort is ongoing. : NCT05470283 and NCT06060613 .”
Published in Nature Medicine · Current Stage: Phase I/II