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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
RM-1995 will be administered by intravenous (IV) infusion followed approximately 24 hours later by tumor illumination with 690 nm non thermal red light using the PIT690 Laser System. The starting dose of RM-1995 will be 0.25 mg/kg and escalated up to 2.0 mg/kg over 6 dosing cohorts
Pembrolizumab (200 mg) will be administered by intravenous (IV) infusion one week before the first RM-1995 PIT treatment and the second dose three weeks later for patients in the combination arm. Once the DLT window is complete, pembrolizumab dosage will be maintained at either 200 mg Q3w, or shift to 400 mg Q6w, per investigator discretion.
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).
Incidence of dose-limiting toxicities (DLTs), frequency of adverse events, and MTD or MAD
Time frame: 24 months
Phase 1b Combination Therapy: Evaluate the safety and tolerability of RM-1995 PIT treatment in combination with pembrolizumab and determine the MTD or MAD.
Incidence of dose-limiting toxicities (DLTs), frequency of adverse events, and MTD or MAD
Time frame: 24 months
Serum concentration of RM-1995.
Time frame: Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days.
Serum concentration of total antibody.
Time frame: Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days.
Serum concentration of IR-700.
Time frame: Various timepoints from Cycles 1, 2, and 3, Day 1 through Day 21. Each cycle is 21 days.
Assess antitumor activity of RM-1995.
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)
Time frame: 24 months
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