RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced CuSCC and HNSCC

Phase 1

Withdrawn

• Conditions: Head and Neck Squamous Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
• Interventions: Combination Product: RM-1995; Biological: Pembrolizumab

• Registration Number: NCT05220748
• Lead Sponsor: Rakuten Medical, Inc.

Brief Summary

A phase 1a/1b, open-label, RM-1995 drug-dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of RM-1995 photoimmunotherapy treatment as monotherapy (phase 1a) or combined with pembrolizumab (phase 1b) in patients with cutaneous squamous cell carcinoma (cuSCC) or head and neck squamous cell carcinoma (HNSCC) that has progressed despite all available standard therapies.

Detailed Description

Enrollment consists of six cohorts of patients with locally advanced cuSCC or HNSCC that has recurred or progressed on or after at least one prior line of therapy, which must include prior platinum-based chemotherapy and is not eligible for further locoregional therapy, or with metastatic disease that has recurred or progressed after all available standard therapies. Patients will receive anti-CD25 antibody, conjugated to the light-activatable dye, IRDye® 700DX, followed by illumination with non-thermal red light (RM-1995 photoimmunotherapy)) as monotherapy (phase 1a), or in combination with pembrolizumab (phase 1b).

Patients are required to have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1,Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a superficial lesion accessible to photoimmunotherapy at the time of screening.

Phase 1a primary objectives are to evaluate the safety and tolerability of RM-1995 photoimmunotherapy treatment as monotherapy and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD).

Phase 1b primary objectives are to evaluate the safety and tolerability of RM-1995 photoimmunotherapy treatment in combination with pembrolizumab and determine the MTD or MAD.

Study Timeline

• Study First Submitted: 2022-01-11
• Study First Submitted QC: 2022-02-01
• Study First Posted: 2022-02-02
• Study Start: 2022-03-24
• Primary Completion: 2023-01-30
• Study Completion: 2023-01-30
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-14
• Last Update Posted: 2023-04-19

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RM-1995 Photoimmunotherapy (Phase 1a Monotherapy)	RM-1995	Patients with locally advanced cuSCC or HNSCC or metastatic disease that has recurred or progressed, despite all available standard therapies.
RM-1995 Photoimmunotherapy + Pembrolizumab (Phased 1b Combination Therapy)	Pembrolizumab	Patients with locally advanced cuSCC or HNSCC or metastatic disease that has recurred or progressed, despite all available standard therapies.
RM-1995 Photoimmunotherapy + Pembrolizumab (Phased 1b Combination Therapy)	RM-1995	Patients with locally advanced cuSCC or HNSCC or metastatic disease that has recurred or progressed, despite all available standard therapies.

Primary Outcome Measures

Name	Time	Method
Phase 1a Monotherapy: Evaluate the safety and tolerability of RM-1995 PIT treatment, and determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD).	24 months	Incidence of dose-limiting toxicities (DLTs), frequency of adverse events, and MTD or MAD
Phase 1b Combination Therapy: Evaluate the safety and tolerability of RM-1995 PIT treatment in combination with pembrolizumab and determine the MTD or MAD.	24 months	Incidence of dose-limiting toxicities (DLTs), frequency of adverse events, and MTD or MAD

Secondary Outcome Measures

Name	Time	Method
Serum concentration of RM-1995.	Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days.
Serum concentration of total antibody.	Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days.
Serum concentration of IR-700.	Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days.
Assess antitumor activity of RM-1995.	24 months	Objective Response Rate (ORRPIT) defined as the proportion of patients with confirmed PIT-treated tumor response of complete response or partial response per RECIST 1.1 (or irRECIST for patients receiving pembrolizumab combination therapy)