RG6232 / Roche - LARVOL DELTA

Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure. (PubMed, Front Oncol) - P1 | "This study provides important insights into how the use of active drug PK assays, coupled with mechanistic follow-up, can inform and enable ongoing benefit/risk assessment for individuals participating in FIH dose-escalation trials. Translational studies that lead to a better understanding of the underlying biology of cognate T- and B-cell interactions, ultimately resulting in ADA development to novel biotherapeutics, are needed."

Journal • Metastases • P1 data • Melanoma • Oncology • Solid Tumor • IL6 • TNFA • Tyrosinase • TYRP1

Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure (Front Oncol) - P1 | N=20 | NCT04551352 | Sponsor: Hoffmann-La Roche | "Twenty participants with cutaneous, uveal, or mucosal TYRP1-positive melanoma received TYRP1-TCB in escalating doses (0.045 to 0.4 mg). All participants experienced ≥1 treatment-related adverse event (TRAE); two participants experienced grade 3 TRAEs. The most common toxicities were grade 1–2 cytokine release syndrome (CRS) and rash. Fractionated dosing mitigated CRS and was associated with lower levels of interleukin-6 and tumor necrosis factor-alpha. Measurement of active drug (dual TYPR1- and CD3-binding) PK rapidly identified loss of active drug exposure in all participants treated with 0.4 mg in a flat dosing schedule for ≥3 cycles."

P1 data • Melanoma

A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jan 2023 ➔ Jul 2022 | Trial primary completion date: Jan 2023 ➔ Jul 2022

Trial completion • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • TYRP1

A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=310 ➔ 20

Enrollment change • Cutaneous Melanoma • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • TYRP1

A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas (clinicaltrials.gov) - P1 | N=310 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Cutaneous Melanoma • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • TYRP1

A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas (clinicaltrials.gov) - P1; N=310; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Sep 2023 ➔ Jan 2023; Trial primary completion date: Sep 2023 ➔ Jan 2023

Clinical • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • TYRP1

A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas (clinicaltrials.gov) - P1; N=310; Recruiting; Sponsor: Hoffmann-La Roche; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cutaneous Melanoma • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • TYRP1

A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas (clinicaltrials.gov) - P1; N=310; Not yet recruiting; Sponsor: Hoffmann-La Roche

Clinical • New P1 trial • Cutaneous Melanoma • Eye Cancer • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • TYRP1