Lamivudine for Solid Tumors

Overseen By Aleksandra Wawrzyniak

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Thomas Marron

Must be taking: PD-(L)1 blockers

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Chemotherapy, Radiotherapy, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Lamivudine for individuals with certain solid tumors that haven't responded to standard cancer immunotherapy. The primary goal is to determine the safety and efficacy of Lamivudine when combined with other treatments that block proteins (PD-1 or PD-L1) that help cancer cells evade the immune system. Suitable candidates have a solid tumor that worsened after immunotherapy and lack other standard treatment options. The trial will also assess how long the treatment can prevent cancer growth and its impact on overall survival. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on chemotherapy, radiotherapy, or investigational agents close to the start of the trial. If you are on certain medications like systemic steroids or immunosuppressive therapy, you may need to adjust or stop them before joining.

Is there any evidence suggesting that Lamivudine is likely to be safe for humans?

Research shows that lamivudine is generally safe for people. Previous studies found it effective for treating hepatitis B, and most patients tolerate it well. No significant increase in major birth defects occurs with lamivudine use.

In some cancer patients, lamivudine has been used to prevent hepatitis B from reactivating, further supporting its safety in various situations.

Overall, the FDA has approved lamivudine for other uses, indicating a strong safety record. However, since this trial tests it for a new use (solid tumors), researchers are carefully studying its effects to ensure it is safe and effective in this new setting. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments that primarily involve immunotherapies like PD-1 or PD-L1 inhibitors, Lamivudine offers a fresh approach. Originally an antiviral medication, Lamivudine is being explored for its potential to target the DNA of cancer cells directly, which might bypass the usual immune pathways. Researchers are excited about Lamivudine because it could provide a new avenue for patients whose tumors have stopped responding to traditional immunotherapies, potentially offering hope where other options have failed.

What evidence suggests that lamivudine might be an effective treatment for relapsed refractory solid tumors?

Research shows that lamivudine primarily treats hepatitis B infections by reducing the risk of the hepatitis B virus (HBV) reactivating, which can lead to serious liver problems. In cancer treatment, studies have explored how lamivudine might enhance effectiveness when combined with other treatments, such as those targeting PD-(L)1, a protein that allows cancer cells to evade the immune system. This trial tests lamivudine with PD-(L)1 blockers to determine if it can enhance the body's ability to combat cancer unresponsive to standard treatments. Early results suggest this combination may benefit patients whose cancer has progressed despite previous treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

Thomas Marron, MD PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for patients with relapsed/refractory metastatic solid tumors that didn't respond to standard PD-(L)1 blockade treatments. It's a small study, aiming to enroll 6-24 participants over two years at Mount Sinai Health System.

Inclusion Criteria

I can care for myself but may not be fully active due to a long-term disability not related to my current illness.

I agree to use birth control during and for 3 months after the study.

My organs and bone marrow are working well.

Exclusion Criteria

I haven't had chemotherapy in the last 14 days.

I have not received a live vaccine in the last 30 days.

I haven't had radiotherapy in the last week, except for palliative care.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1b

Determine the safety and tolerability of Lamivudine with continued PD-(L)1 blockade for patients with relapsed/refractory metastatic solid tumors

21 days per cycle

Cycle 1, each cycle is 21 days

Treatment Phase 2

Determine the effect of adding lamivudine to PD-(L)1 blocking agents in patients with relapsed/refractory solid tumors

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Lamivudine
• PD-L1 Blocker

Trial Overview The trial is testing the safety and effectiveness of Lamivudine when added to ongoing PD-L1 blocker therapy in patients whose solid tumors have not improved with previous treatments. The goal is to see if this combination can better control tumor growth.

How Is the Trial Designed?

Group I: Participants with Relapsed Refractory Solid Tumors Experimental Treatment 2 Interventions

Participants with Solid Tumors which are typically treated with cancer immunotherapy (PD-1 or PD-L1 blocking antibodies) and their cancer has progressed on immunotherapy will be candidates for the trial. This is a single-arm trial.

Lamivudine is already approved in United States, European Union for the following indications:

Approved in United States as Epivir for:

• HIV infection
• hepatitis B (HBV) infection

Approved in European Union as Epivir for:

• HIV infection
• hepatitis B (HBV) infection

Who Is Running the Clinical Trial?

Thomas Marron

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

Immune checkpoint inhibitors have shown significant survival benefits over traditional chemotherapy for patients with solid organ cancers, highlighting their growing importance in cancer treatment.

The review emphasizes the need for biomarkers, such as PD-L1 expression and tumor mutational burden, to better select patients for these therapies, particularly in cancers like lung and urothelial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers for immune checkpoint inhibitors in solid tumors. Kapoor, V., Kelly, WJ.[2023]

In a study using an orthotopic liver cancer model, the combination of lenalidomide and sorafenib significantly improved anti-tumor efficacy, leading to delayed tumor growth and increased survival in treated animals.

The enhanced anti-tumor effect was linked to an increase in CD8(+) T cells that produce interferon-γ, indicating that lenalidomide boosts the immune response against tumors when used with sorafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential synergistic anti-tumor activity between lenalidomide and sorafenib in hepatocellular carcinoma. Ou, DL., Chang, CJ., Jeng, YM., et al.[2022]

In a study of 519 patients with HBeAg-positive chronic hepatitis B treated with lamivudine for an average of 20 months, 37% achieved HBeAg seroconversion, indicating effective suppression of the virus.

Predictive factors for successful HBeAg seroconversion included decreasing HBeAg levels during treatment, initial HBeAg levels, ALT levels, and the duration of therapy, highlighting the importance of monitoring these variables for treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Predictive factors and efficacy of lamivudine treatment in chronic hepatitis B infection]. Park, NH., Shin, JW., Park, JH., et al.[2017]

In a study of 148 chronic hepatitis B patients, those with hepatitis B virus-related hepatocellular carcinoma (HCC) showed significant improvements in liver function after 12 months of lamivudine treatment, including increased albumin levels and decreased ascites and Child-Pugh scores.

Lamivudine demonstrated comparable antiviral effects in both patients with HCC and those without, suggesting that effective treatment of hepatitis B may enhance the potential for curative therapies in patients with HBV-related HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of lamivudine on hepatitis B viral status and liver function in patients with hepatitis B virus-related hepatocellular carcinoma. Kim, JH., Park, JW., Koh, DW., et al.[2013]

Preventive lamivudine significantly reduces the risk of hepatitis B virus (HBV) reactivation and related complications in cancer patients undergoing chemotherapy, with a relative risk for HBV reactivation ranging from 0.00 to 0.21 based on 14 studies involving 275 patients on lamivudine and 475 controls.

None of the patients receiving preventive lamivudine developed HBV-related hepatic failure, and there were significantly fewer deaths attributed to HBV in the lamivudine group (4 deaths) compared to the control group (27 deaths), indicating its efficacy and safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Loomba, R., Rowley, A., Wesley, R., et al.[2022]

Lamivudine has been an effective treatment for chronic hepatitis B since its FDA approval in 1998, particularly for patients who are hepatitis B e antigen-positive.

However, a significant challenge is the development of drug-resistant mutants, which occur in 15 to 30% of patients each year, leading to potential relapse and complications, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lamivudine for chronic hepatitis B. Leung, N.[2021]

Prophylactic use of lamivudine significantly reduces the risk of hepatitis B virus (HBV) reactivation in solid tumor patients undergoing systemic chemotherapy, with a relative risk of 0.17 based on a meta-analysis of 1,101 patients.

Lamivudine not only lowers the risk of HBV reactivation but also decreases related negative outcomes such as hepatitis, chemotherapy disruptions, and potentially mortality, highlighting its efficacy as a preventive measure in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic effect of lamivudine on chemotherapy-induced hepatitis B virus reactivation in patients with solid tumour: A meta-analysis. Xu, Z., Dai, W., Wu, YT., et al.[2018]

Recent phase 3 trials have shown that targeted and immune-based therapies significantly improve treatment outcomes for patients with hepatocellular carcinoma, indicating a shift in treatment options.

Several new agents targeting specific pathways and immune checkpoints are currently in clinical development, with some already awaiting FDA approval or recently approved for use as first- and second-line therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted and Immune-Based Therapies for Hepatocellular Carcinoma. Greten, TF., Lai, CW., Li, G., et al.[2023]

Gemcitabine treatment enhances the immune response in hepatocellular carcinoma (HCC) by increasing the infiltration of T cells and reducing suppressive immune cells, without significantly inhibiting tumor growth on its own.

The combination of gemcitabine with PD-1 blockade significantly reduces tumor volume and prevents relapse in HCC, indicating that this combination therapy is more effective than either treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-facilitated modulation of the tumor microenvironment and PD-1/PD-L1 blockade generate a synergistic antitumor effect in a murine hepatocellular carcinoma model. Wang, H., He, X., Fang, D., et al.[2022]

Sorafenib was the first systemic therapy proven to improve survival in patients with advanced hepatocellular carcinoma (HCC), but recent treatments like lenvatinib and anti-PD-1 antibodies are emerging as effective options.

Combination therapies using anti-PD-1 antibodies with anti-angiogenesis agents are showing enhanced anti-tumor effects in early clinical trials, indicating a promising direction for future HCC treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging agents and regimens for hepatocellular carcinoma. Zhu, XD., Sun, HC.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06494579

Study Details | NCT06494579 | Lamivudine for Solid Tumors Single arm, set dose clinical trial of Lamivudine for Relapsed Refractory Solid Tumors. Accrual 6-24 patients, within 2 years, study completion within 3 ...

2. mountsinai.org mountsinai.org/clinical-trials/lamivudine-for-solid-tumors

Lamivudine for Solid Tumors - Clinical Trials 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.

3. withpower.com withpower.com/trial/phase-2-neoplasms-7-2024-02aa9

Lamivudine for Solid Tumors Lamivudine not only lowers the risk of HBV reactivation but also decreases related negative outcomes such as hepatitis, chemotherapy disruptions, and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3437537/

Management of hepatitis B reactivation in patients ... Adefovir has lower primary resistance rates and has been shown to be effective against lamivudine-resistant HBV strains. Two case reports of successful adefovir ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29265535/

Prophylactic effect of lamivudine on chemotherapy-induced ... The primary outcome was HBV reactivation, and the secondary outcomes were HBV-related hepatitis, chemotherapy disruption, mortality and tyrosine-methio-nine- ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/021003s020lbl.pdf

EPIVIR-HBV safely and effectively. - accessdata.fda.gov Risk Summary. Available data from the APR show no substantial difference in the risk of overall major birth defects for lamivudine compared with the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2704311/

Effect of prophylactic lamivudine for chemotherapy ... We found that lamivudine prophylaxis is associated with a significant reduction in hepatitis B virus reactivation (RR 0.21, 95%CI 0.13–0.35) and a trend in ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/020564s37_020596s036lbl.pdf

EPIVIR (lamivudine) - accessdata.fda.gov Limited, uncontrolled pharmacokinetic and safety data are available from administration of lamivudine (and zidovudine) to 36 infants aged up to 1 week in 2 ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)36537-8/fulltext

Hepatitis B virus reactivation in patients with solid tumors ... Hepatitis B virus (HBV) reactivation is a well-known risk during chemotherapy for hematological malignancies with reported rates ranging between 14% and 72%.