Dostarlimab for Colon Cancer

(NAIO Trial)

Overseen by Saima Sharif, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Iowa

Must not be taking: Immunosuppressants, Glucocorticoids

Disqualifiers: Active malignancies, Autoimmune disease, HIV, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing the immunotherapy drug dostarlimab in patients with Stage II and III colon cancer. The goal is to see if the drug can shrink the tumors enough to avoid surgery. Dostarlimab helps the immune system attack the cancer cells.

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.

What data supports the effectiveness of the drug dostarlimab for colon cancer?

Dostarlimab has shown promising results in treating mismatch repair-deficient rectal cancers, with a study reporting a 100% remission rate. This suggests potential effectiveness for similar conditions like colon cancer, especially if they share genetic characteristics. ^{1 2 3 4 5}

Is dostarlimab safe for humans?

Dostarlimab has been approved for use in certain cancers, and studies have shown it to be generally well tolerated in humans, with clinical trials indicating it is safe for use in treating advanced cancers. It has been tested in both animal models and human trials, showing promising safety results. ^{1 2 3 6 7}

How is the drug dostarlimab unique for treating colon cancer?

Dostarlimab is unique because it is a PD-1 monoclonal antibody that has shown a 100% remission rate in a trial for rectal cancer, allowing patients to avoid chemotherapy, radiotherapy, or surgery, which are the usual treatments. ^{1 2 3 5 8}

Research Team

Saima Sharif, MD

Principal Investigator

University of Iowa Holden Comprehensive Cancer Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Dostarlimab (PD-1 Inhibitor)

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.

Participant Groups

Group I: Neoadjuvant Dostarlimab Experimental Treatment 1 Intervention

Participants will receive Dostarlimab 500 mg IV every 3 weeks for 9 cycles followed by 1000 mg every 6 weeks for 12 cycles until 2 years

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Dr. Afable

University of Iowa

Chief Medical Officer since 2005

MD from Loyola Stritch School of Medicine, MPH from the University of Illinois

Joel Harris

University of Iowa

Chief Executive Officer since 2023

B.A. in Economics from the University of Iowa, Post-baccalaureate Certificate in Narrative Communications from Northwestern University

Findings from Research

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]

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 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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2023]

6. United States 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. [2023]

7. United States 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. [2022]

8. England 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. [2022]