Dostarlimab for Colon Cancer

(NAIO Trial)

Overseen By Alisha Demsky

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Iowa

Must not be taking: Immunosuppressants, Glucocorticoids

Disqualifiers: Active malignancies, Autoimmune disease, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests dostarlimab, a medication, to determine if it can improve treatment outcomes for people with Stage II or III colon cancer. Researchers aim to find out if dostarlimab can shrink tumors enough to avoid surgery after 18 weeks of treatment. Individuals with biopsy-confirmed Stage II or III colon cancer that might be surgically removed, and who are open to potentially skipping surgery if the treatment proves effective, may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or have an active autoimmune disease requiring treatment, you may not be eligible to participate.

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

Research shows that dostarlimab, a treatment under study for colon cancer, appears safe. Previous studies on dostarlimab in patients with colorectal cancer showed positive results and were generally well-tolerated. Some patients experienced side effects, but these were mostly mild to moderate.

Dostarlimab is a monoclonal antibody that helps the immune system find and fight cancer cells. The FDA has recognized its potential benefits for certain types of rectal cancer, indicating confidence in its safety.

Additionally, dostarlimab is already approved for treating other cancers, supporting the idea that it is relatively safe. Overall, while no treatment is without risks, dostarlimab seems to be a promising option with a manageable safety profile based on current data. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colon cancer?

Dostarlimab is unique because it targets colon cancer by blocking a protein called PD-1, which helps cancer cells hide from the immune system. Unlike traditional chemotherapy, which attacks rapidly dividing cells broadly, dostarlimab specifically enhances the body's immune response to fight cancer cells. Researchers are excited because this targeted approach may offer a more precise treatment with potentially fewer side effects. Additionally, dostarlimab's dosing schedule—every three weeks initially, then every six weeks—could provide a convenient alternative for patients compared to more frequent chemotherapy sessions.

What evidence suggests that dostarlimab might be an effective treatment for colon cancer?

Studies have shown that dostarlimab effectively treats certain types of cancer. In one study, all patients with a specific type of rectal cancer showed no signs of the disease after treatment. Another trial found that patients with advanced rectal cancer went into complete remission, highlighting the drug's strong potential. Dostarlimab blocks a protein called PD-1, which cancer cells use to hide from the immune system. This action helps the body's defenses fight cancer more effectively. While these results are promising, they mainly involve rectal cancer. Its effectiveness in colon cancer is still under investigation in this trial, where participants will receive neoadjuvant dostarlimab. ^{1 6 7 8 9}

Who Is on the Research Team?

Saima Sharif, MD

Principal Investigator

University of Iowa Holden Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Stage II or III colon cancer that hasn't spread, can be surgically removed, and has a specific abnormality called dMMR. Participants must have normal organ function tests, understand the study requirements, and agree to use contraception. Those with recent major surgery, live vaccines, other cancers within two years, uncontrolled illnesses, certain infections like HIV/HBV/HCV or active autoimmune diseases are excluded.

Inclusion Criteria

My colon cancer biopsy has enough tissue for the required tests.

Contraception requirements for males of reproductive potential

My recent scans show no signs of cancer spread.

Exclusion Criteria

Active autoimmune disease that has required systemic treatment in the past 2 years

I do not have a tumor that is blocking any organs.

I have not had any other major cancers in the last two years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive Dostarlimab 500 mg IV every 3 weeks for 9 cycles followed by 1000 mg every 6 weeks for 12 cycles

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab

Trial Overview The trial is testing Dostarlimab's effectiveness in shrinking colon cancer before surgery. Patients will receive up to six cycles of Dostarlimab over 18 weeks and their response will be monitored to see if they can avoid surgery.

How Is the Trial Designed?

Group I: Neoadjuvant Dostarlimab Experimental Treatment 1 Intervention

Participants will receive Dostarlimab 500 mg IV every 3 weeks for 6 cycles followed by 1000 mg every 6 weeks for 8 cycles until 1.5 years

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?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Published Research Related to This Trial

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, 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 phase II trial involving 12 patients with mismatch repair-deficient, locally advanced rectal cancer, dostarlimab resulted in a remarkable 100% clinical complete response, with no disease progression or recurrence observed so far.

All patients treated with dostarlimab did not require traditional treatments like chemotherapy, radiotherapy, or surgery, suggesting a potentially groundbreaking approach to cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel trial methodology to test interventions with very large effect sizes: the case of dostarlimab in mismatch repair-deficient, locally advanced rectal cancer. Powell, K., Olivier, T., Prasad, V.[2022]

Dostarlimab, a humanized anti-PD-1 antibody, has shown significant antitumor activity in humanized mouse models by enhancing T-cell functions and increasing immune cell infiltration, indicating its potential effectiveness in cancer treatment.

In clinical trials, dostarlimab was well tolerated and received FDA approval for treating adult patients with mismatch repair-deficient recurrent or advanced endometrial cancer, demonstrating its safety and efficacy in a specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models. Kumar, S., Ghosh, S., Sharma, G., et al.[2022]

Neoadjuvant treatment with the immunotherapy dostarlimab has shown remarkable clinical responses in patients with mismatch repair (MMR)-deficient rectal cancers, potentially allowing some patients to avoid surgery altogether.

This study highlights the efficacy of dostarlimab as a promising treatment option for this specific type of rectal cancer, suggesting a significant advancement in cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defying all odds in MMR-deficient rectal cancers. Chalabi, M.[2022]

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]

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 (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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9289402/

Jemperli (Dostarlimab-gxly): An unprecedented cancer trial Recently, it was known to have had a positive effect on treatment of colorectal cancer according to data from a phase 2 clinical trial; 12 patients with stage ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2201445

PD-1 Blockade in Mismatch Repair–Deficient, Locally ... In our study, single-agent dostarlimab was remarkably effective in mismatch repair–deficient, locally advanced rectal cancer, providing a ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842824001173

Dostarlimab: Review on success story and clinical trials A recently published clinical trial reported 100 % remission of advanced rectal cancer without significant side effects in the participants.

4. gsk.com gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-trial-continues-to-show-unprecedented-results/

Jemperli (dostarlimab) trial continues to show ... Jemperli (dostarlimab) trial continues to show unprecedented results with no evidence of disease in 100% of patients with locally advanced ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05723562

A Study of Dostarlimab in Untreated dMMR/MSI-H Locally ... The purpose of this study is to investigate dostarlimab monotherapy in participants with locally advanced Mismatch-repair deficient (dMMR)/Microsatellite ...

6. gsk.com gsk.com/media/tbpjzzcy/jemperli-fda-btd-press-release-161224.pdf

jemperli-fda-btd-press-release-161224.pdf Jemperli (dostarlimab) receives US FDA Breakthrough. Therapy Designation for locally advanced dMMR/MSI-H rectal cancer.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02715284

NCT02715284 | Study of TSR-042, an Anti-programmed ... Part 2B of the study will examine the safety and clinical activity of dostarlimab in cohorts of participants with specific types of advanced solid tumors.

8. mayoclinic.org mayoclinic.org/drugs-supplements/dostarlimab-gxly-intravenous-route/description/drg-20514856

Dostarlimab-gxly (intravenous route) - Side effects & uses Dostarlimab-gxly is a monoclonal antibody that changes the immune system to help control the growth of cancer cells.

9. aetna.com aetna.com/cpb/medical/data/900_999/0993.html

Dostarlimab-gxly (Jemperli) - Medical Clinical Policy Bulletins Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of colorectal cancer, including appendiceal adenocarcinoma and ...