Lamivudine for Solid Tumors

ID#: NCT06494579

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 1/Phase 2

Recruitment Status: Recruiting

Start Date: September 30, 2024

End Date: July 15, 2027

Contact Information:
Aleksandra Wawrzyniak
(212) 824-7437
Summary: 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).
Eligibility:

Inclusion Criteria:

- Patients must have a pathologically confirmed diagnosis of a solid malignancy

- Patients must have progressed (clinically or radiographically) on or following prior therapy with a PD-1 or PD-L1 targeted antibody

- Patients must have exhausted or declined all standard therapies deemed to have significant clinical benefit

- Patients may have only 0 or 1 intervening lines of therapy from the prior PD-(L)1 blocking therapy

- Patient must be willing and able to provide blood samples (12 green-top tubes, roughly 100mL) at the four time points indicated in the Study Calendar.

- Age ≥ 18 years.

- ECOG 0-2. The exception will be patients carrying long term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy. This must be documented in screening clinic visit note by investigator.

- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 24 consecutive months

- Ability to understand and the willingness to sign a written informed consent.

- Adequate organ and marrow function Exclusion Criteria

- Patients who have had chemotherapy within 14 days from start of therapy.

- Patients who have had radiotherapy within 7 days from start of therapy, though exception may be made for palliative radiotherapy which is permitted at anytime, if deemed in the best interest of the patient.

- Patients may not be receiving any other investigational agents.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

- Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Exception: Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.

- Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Exception: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is acceptable.

- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.

- Known HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen, or with <350 CD4+ T cells/microliter in the peripheral blood. HIV testing is not required for patients with no known history of HIV.

- Any patient already on antiretroviral therapy

- Has known Hepatitis B or active Hepatitis C (e.g., HCV RNA [qualitative] is detected). HBV and HCV testing is not required for patients with no known history of these viruses.

- History of allogeneic hematopoietic cell transplantation or solid organ transplantation.

- Receipt of a live vaccine within 30 days of planned start of study drug

- Documented allergic or hypersensitivity response to any protein therapeutics (e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal antibodies, receptor traps). Principal investigator believes that for one or multiple reasons the patient will be unable to comply with all study visits, or if they believe the trial is not clinically in the best interest of the patient.

- History of irAE in response to prior immunotherapy that has not improved to a Grade 0 or 1; this does not include chronic conditions such as endocrinopathies which can be treated with hormone replacement therapy.

- History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis attributed to prior use of cancer immunotherapy that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted.