Dostarlimab + LB-100 for Ovarian Cancer

Overseen By Amir Jazaeri, M D

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Active infection, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 months

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of two drugs, dostarlimab (an immunotherapy drug) and LB-100, can help manage ovarian clear cell carcinoma, a type of ovarian cancer. Participants will receive the treatments intravenously over several days in each cycle. Eligible participants should have recurrent clear cell ovarian cancer that has returned after at least one previous treatment or is resistant to platinum-based therapies. The trial will focus on those with a measurable tumor that can be tracked over time. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you cannot have any concurrent chemotherapy, immunotherapy, or hormonal therapy for cancer treatment. It's best to discuss your current medications with the study team to see if they might interfere with the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dostarlimab is generally well-tolerated in other studies. This treatment, known as immunotherapy, aids the body's immune system in fighting cancer. Common side effects include fatigue, nausea, and diarrhea, but these are usually manageable.

LB-100 has undergone less study, but early research suggests it can be administered safely. Some side effects include low blood cell counts and mild nausea.

Specific safety information for using dostarlimab and LB-100 together is not yet available. As this trial is in its early stages, the safety of the treatment remains under investigation. The trial aims to determine how well patients tolerate the combination and identify potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of dostarlimab and LB-100 for ovarian cancer because it brings a fresh approach to treatment. Dostarlimab is a checkpoint inhibitor that helps the immune system recognize and attack cancer cells, which is different from traditional chemotherapy that directly targets and kills cancer cells. LB-100 is a novel agent that blocks a specific enzyme, potentially enhancing the effectiveness of dostarlimab and overcoming resistance to other treatments. This combination holds promise for improving outcomes by harnessing the body’s immune response and introducing a new mechanism of action to combat ovarian cancer.

What evidence suggests that the combination of dostarlimab and LB-100 might be an effective treatment for ovarian cancer?

Research has shown that combining dostarlimab and LB-100, which participants in this trial will receive, may help treat ovarian clear cell carcinoma. Dostarlimab enhances the immune system's ability to attack cancer cells, while LB-100 weakens cancer cells, making them easier to destroy. Early results suggest that this combination could enhance the effectiveness of immunotherapy, potentially improving survival rates for patients with this type of cancer. Although this research remains in the early stages, it could offer new hope for those facing this challenging condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with recurrent clear cell ovarian, peritoneal, or fallopian tube cancer who've had prior treatment or are platinum-resistant. They must have measurable disease and good organ/bone marrow function. Women of childbearing potential must use contraception due to unknown effects on fetuses.

Inclusion Criteria

Your platelet count is greater than or equal to 100 x 109/L (more than 100,000/mm3).

I am considered post-menopausal due to not having periods for 12 months without other medical reasons.

I am willing and able to follow the study's treatment and visit schedule.

Exclusion Criteria

Concurrent treatment on another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

Subjects with irreversible toxicity not reasonably expected to be exacerbated by the treatment with investigational therapy may be included only after consultation with the primary investigator

You have celiac disease, but it is managed well with a special diet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dostarlimab and LB-100. Dostarlimab is given by vein on Day 1 of each cycle, and LB-100 is given by vein on Days 1-3 of each cycle.

6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and progression-free survival.

6-12 months

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab
• LB-100

Trial Overview The trial tests the combination of dostarlimab and LB-100 in controlling ovarian clear cell carcinoma. Participants will receive both drugs to see if this duo is more effective than current treatments.

How Is the Trial Designed?

Group I: Dostarlimab + LB-100 Experimental Treatment 2 Interventions

Dostarlimab will be given by vein over about 30 minutes on Day 1 of each cycle. LB-100 will be given by vein on Days 1-3 of each cycle. The first doses will be given over about 2 hours. After that, doses may be given over as little as 30 minutes.

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

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
• dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen

Approved in United States as Jemperli for:

• Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
• Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

GSK Pharma

Collaborator

Trials

1

Recruited

20+

Lixte

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

Dostarlimab, an anti-PD-1 monoclonal antibody, has been shown to be equipotent to pembrolizumab in suppressing PD-1 activity, with an estimated effective concentration of 1.95 μg/ml based on data from the GARNET trial.

The recommended dosing regimen for dostarlimab is 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks, which supports its use as a potent treatment option for patients with recurrent or advanced mismatch repair-deficient solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. Austin, D., Melhem, M., Gandhi, Y., et al.[2023]

In a study involving 478 patients, dostarlimab, an anti-PD-1 monoclonal antibody, showed a low incidence of treatment-emergent antidrug antibodies (ADAs) at 2.5%, indicating a favorable safety profile compared to other similar therapies.

Despite the presence of ADAs in a small number of patients, there was no evidence of reduced efficacy or safety for dostarlimab, supporting its use as an effective treatment for various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Integrated Analysis of Dostarlimab Immunogenicity. Lu, S., Bowsher, RR., Clancy, A., et al.[2022]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab showed promising antitumor activity in patients with recurrent/advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based chemotherapy, achieving an immune-related objective response rate (irORR) of 26.9% across various PD-L1 expression levels.

The treatment was generally well-tolerated, with fatigue being the most common severe adverse event (4.5%), and immune-related treatment-emergent adverse events occurring in 28.4% of patients, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Moreno, V., Roda, D., Pikiel, J., et al.[2023]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-07922

Dostarlimab and LB-100 for the Treatment of Patients with ... Giving dostarlimab and LB-100 may kill more tumor cells in patients with recurrent ovarian clear cell carcinoma, peritoneal, or fallopian tube cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06065462

NCT06065462 | Safety and Efficacy of Targeting PP2A in ... Primary Objectives: 1. To estimate overall survival in patients with recurrent ovarian clear cell carcinoma being treated with LB-100 and dostarlimab, ...

3. ir.lixte.com ir.lixte.com/news-events/press-releases/detail/101/first-patient-dosed-with-lixtes-lb-100-and-gsks-immunotherapy-dostarlimab-gxly-in-ovarian-clear-cell-carcinoma-trial

First Patient Dosed with LIXTE's LB-100 and GSK's ... ... dostarlimab-gxly, may enhance the effectiveness of immunotherapy in the treatment of ovarian clear cell carcinoma (OCCC). The clinical trial ...

4. withpower.com withpower.com/trial/phase-2-carcinoma-2-2024-fcc38

Dostarlimab + LB-100 for Ovarian Cancer Dostarlimab boosts the immune system to fight cancer, and LB-100 makes cancer cells easier to kill. The goal is to see if this combination can control the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06065462?term=AREA%5BInterventionSearch%5D(LB-100)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=6

Safety and Efficacy of Targeting PP2A in Ovarian Clear ... To estimate overall survival in patients with recurrent ovarian clear cell carcinoma being treated with LB-100 and dostarlimab, including specific survival ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40461381/

Dostarlimab and niraparib in primary advanced ovarian ... 1. The key secondary endpoint was overall survival (OS). Safety was assessed in patients who received one or more doses of study treatment (arms ...