Early Phase II Exploratory, Open-Label, Non-Randomized Study of Neoadjuvant Dostarlimab Monotherapy in Participants with Untreated T3-4N0-2 or Stage III pMMR/MSS Resectable Colon Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]

Trial duration

3 Apr 2025 → ongoing

Decision date (initial)

2024-12-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GSK

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The trial aims to generate data on the multi-omic changes due to neo-adjuvant dostarlimab monotherapy in participants with untreated T3-4N0-2 or Stage III pMMR/MSS resectable colon cancer and create a reference omics database.

Secondary objectives 2

1. To evaluate the feasibility and tolerability of neo-adjuvant dostarlimab monotherapy in participants with untreated T3-T4N0 or Stage III (resectable) pMMR/MSS colon cancer.
2. Proportions of responders (iRECIST) and survivors at 2 years will be reported

Conditions and MedDRA coding

pMMR/MSS resectable Colon Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Untreated, pathologically confirmed colon adenocarcinoma
2. Clinically staged cT3-4, cN0-2, cM0 or stage III
3. Resectable primary tumour, and fit to undergo resection
4. MMR-p by IHC or not MSI-H by PCR (or microsatellite testing)
5. Voluntary written informed consent (ICF) of the participant or their legally authorized representative obtained prior to any screening procedures. Patient agrees to provide tumour tissue obtained during colonoscopy (ies) and surgery and necessary blood samples.
6. Tumour and normal tissue samples from biopsies are available, collected either from a standard diagnostic colonoscopy in pre-screening or a repeat colonoscopy in screening. Note: Cytological specimens such as fine needle aspirates or cell blocks are not acceptable.
7. At least 18 years of age at the time of signing the Informed Consent.
8. Use of highly effective methods of birth control for the duration of the trial treatment and for 120 days after the last dose of immunotherapy; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the trial treatment(s)) or commitment to a vasectomised partner.
9. Extra: A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
10. ECOG performance status 0-1
11. Adequate bone marrow, renal and liver function as well as coagulation allowing patients to undergo neoadjuvant immunotherapy

Exclusion criteria 23

1. Metastatic disease
2. History of (non-infectious) pneumonitis/interstitial lung disease that required steroids, or current pneumonitis /interstitial lung disease
3. Participant has active autoimmune disease that required systemic treatment in the past 2 years, is immunocompromised in the opinion of the Investigator, or is receiving systemic immunosuppressive treatment. (Note: Participants with splenectomy are allowed.) Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
4. Participant has received systemic steroid therapy (>10 mg daily prednisone or equivalent) within 7 days prior to the first dose of the study treatment or is receiving any other form of immunosuppressive medication. Replacement therapy is not considered a form of systemic therapy. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.
5. Participant has an active infection requiring systemic steroid therapy within 1 week prior to the anticipated first dose of study treatment.
6. Has a known history of [or has a positive test result at Screening for] HIV infection HIV infection, with the exception of participants who are positive for HIV and meet all of the following criteria: a. Is receiving a stable regimen of HAART; Must be on an uninterrupted combination antiretroviral therapy regimen for at least 3 months prior to screening, with combination antiretroviral therapy regimen consistent with locally rec guidelines b. Has no requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; an c. Has a CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests. CD4+ counts >/= 350 cells/microL over past 12 months and at a screening and not measurement of less than 350 cells /mm3 during that time period Documented evidence of plasma HIV-1 RNA persistently less than 50 copies /mL confirmed </= 3 months prior to AND at Screening ; unless undetectable viral load is defined differently by local guidelines and agreed with the sponsor’s medical monitor. In the > 3 to 12 months prior to screening plasma HIV-1 RNA consistently <50 c/mL required; if single/isolated increased >/= 50 c/mL occurred, and are thought not to be persistent, not associated with antiretroviral resistance as per investigator assessment, the patient would be eligible.
7. Known hepatitis B or C infection. Participants with a negative HbsAg and positive HbcAb are eligible only if HBV DNA is negative. Participants with a positive HCV antibody due to prior resolved disease can be enrolled only if a confirmatory negative HCV RNA test is obtained
8. Participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. Note: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
9. Known Mycobacterium tuberculosis infection
10. Allogenic tissue/solid organ transplant
11. Known psychiatric or substance abuse disorder that would interfere with patient’s ability to cooperate with the requirements of the trial
12. Previous line of treatment for colon cancer (chemotherapy, immunotherapy, biologic, or targeted therapy, radiation therapy or surgery)
13. Prior malignancy active within the previous 3 years, with the exception of adequately treated basal or squamous skin cancer, cervical carcinoma in situ, superficial bladder cancer without evidence of disease, other in situ cancers, or had a malignancy treated with curative intent and with no evidence of disease recurrence for 2 years since the initiation of that therapy.
14. Participation in another interventional trial with an investigational medicinal product (IMP) or device
15. Use of any other treatment(s) that might jeopardise the participant’s safety or that would compromise the integrity of the trial, including prior use of immunotherapy for other malignancy.
16. Receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy
17. Any disorder, which in the investigator’s opinion might jeopardise the participant’s safety or compliance with the protocol (e.g history of allergy or hypersensitivity to trial drug components, bowel obstruction, peritonitis, other active malignancies)
18. Participant has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies or fusion proteins, sensitivity to any of the study treatments or components thereof, or a history of drug or other allergy that contraindicates their participation.
19. Is immunocompromised in the opinion of the Investigator. Diagnosis of any immunodeficiency including active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
20. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a. Is not a woman of childbearing potential (WOCBP). Or b. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), from the Screening Visit through at least 120 days after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. c. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) within 24 hours prior to the first dose of study treatment. The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
21. Has a history of or evidence of serious, uncontrolled cardiac arrhythmia or clinically significant cardiac disease within the 6 months prior to enrollment.
22. Prior / concomitant therapy. Patient is excluded in the following circumstances: • Has received treatment with an investigational agent within [4 weeks] of the first dose of study intervention. Note: this refers to agents for diagnoses that do not fall under the categories of cancers or autoimmunity. • Is receiving immunosuppressive medication. • Has received systemic corticosteroids (>10 mg daily prednisone or equivalent) within 7 days of first dose of study intervention. Use of inhaled steroids, local injection of steroids, topical steroids, and steroidal eye drops are allowed. • Has previously received any therapies for their colon cancer. Note: If such therapy was used for a prior cancer diagnosis, the last dose of anti-PD(L)1 must be 2 years prior to C1D1. • Has received any live vaccine within 30 days of enrollment. Vaccination against COVID-19 using vaccines that are authorized via the appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional Marketing Authorization, or Marketing Authorization Application) are not exclusionary. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live. If a COVID-19 vaccine is administered at any time, the date of COVID-19 vaccination must be entered in the eCRF.
23. Participant has experienced any of the following with prior immunotherapy: any immune related AE (irAE) of Grade 3 or higher, immune-related severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain Barré syndrome, or transverse myelitis), exfoliative dermatitis of any grade (SJS, TEN, or DRESS syndrome), or myocarditis of any grade. Non–clinically significant laboratory abnormalities are not exclusionary

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Data generation through multi-omic exploration of blood and tissue derived products. Correlation of molecular-biological features identified with pathological response.

Secondary endpoints 4

1. Safety analysis. Frequency and severity of treatment emergent AEs, SAEs, irAEs. AEs leading to death, discontinuation of trial intervention or resulting in the participant not being suitable for surgery.
2. Proportion of participants with pathological response, determined by local assessment.
3. Survival time defined from Superhero ICF signature to death from any cause. Proportion of survivors at 2 years.
4. Event free survival time (EFS) defined from Superhero ICF signature to recurrence evaluated by local assessment or death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Sabine Tejpar

Public contact point

Organisation

UZ Leuven

Contact name

Sabine Tejpar

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications