Single arm, set dose clinical trial of Lamivudine for Relapsed Refractory Solid Tumors. Accrual 6-24 patients, within 2 years, study completion within 3 years at Mount Sinai Health System. Primary Objective: For Phase 1b to determine the safety and tolerability of Lamivudine with continued PD-(L)1 blockade for patients with relapsed/refractory metastatic solid tumors that have progressed on standard PD-(L)1 blockade. For Phase 2, to determine the effect of adding lamivudine to PD-(L)1 blocking agents in patients with relapsed/refractory solid tumors that have progressed on prior PD-(L)1 agents Secondary Objectives (Phase 1b and 2) Assess 1) Safety and Tolerability, 2) Best overall response rate (BORR), 3) Progression-free survival (PFS), 4) Overall survival (OS) and 5) Duration of response following addition of lamivudine to standard PD-(L)1 blocking agents, 6) Disease control rate (DCR).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Lamivudine is used in the management of human immunodeficiency virus (HIV) and Hepatitis B Virus. It is being repurposed here to assess if this can improve response to cancer immunotherapy
PD-1 or PD-L1 blocking antibodies; there are around a dozen of these FDA approved for varying indications, and whatever is administered to a patient as standard of care (FDA APPROVED) will be continued in the patients and administered in combination with lamivudine.
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Dose limiting toxicity (DLTs) per CTCAE Version 5.0
Dose-limiting toxicity rate in the first 6 patients based on the CTCAE version 5.0. DLTs were defined as any Lamivudine-related Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0) Grade 3 or 4 adverse events.
Time frame: Cycle 1, each cycle is 21 days
DLT of combined treatment of lamivudine and PD-(L)1 targeted therapy.
To determine the safety and tolerability of combined treatment of lamivudine and PD-(L)1 targeted therapy in patients with relapsed or refractory solid tumors. DLTs were defined as any treatment-related Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0) Grade 3 or 4 adverse events.
Time frame: Cycle 1, each cycle is 21 days
Best overall response rate (BORR).
Best overall response rate (BORR), defined as the percent of patients achieving a Complete Response (CR) or Partial Response (PR) on initial or subsequent imaging before initiation of subsequent line of anti-cancer therapy
Time frame: End of study at 3 years
Overall survival (OS)
Overall survival (OS): defined as the time from the first dosing of lamivudine and date of death
Time frame: End of study at 3 years
Progression free survival (PFS):
Progression free survival (PFS): defined as the time from first dosing of lamivudine to date of objectively documented progression of disease or death
Time frame: End of study at 3 years
Duration of response (DOR)
Duration of response (DOR): defined as the time between the date of first response of CR or PR to the date of first documented tumor progression or death due to any cause
Time frame: End of study at 3 years
Disease control rate (DCR)
Disease control rate (DCR): defined as percent of patients experiencing CR, PR or Stable Disease (SD) at the time of first imaging.
Time frame: End of study at 3 years
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