Phase 3 study of perioperative dostarlimab in participants with untreated T4N0 or stage III dMMR/MSI-H resectable colon cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Nov 2023 → ongoing

Decision date (initial)

2023-09-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The Primary objective is to evaluate the efficacy of peri-operative dostarlimab compared with standard of care in participants with untreated T4N0 or Stage III (resectable), dMMR/MSI-H colon cancer.

Secondary objectives 6

1. Secondary objectives for this patient population with untreated T4N0 or Stage III (resectable), dMMR/MSI-H colon cancer are: To evaluate the efficacy of neo-adjuvant dostarlimab in participants.
2. To estimate the difference in overall survival for participants treated with perioperative dostarlimab compared with Standard of care (SOC).
3. To evaluate the efficacy of peri-operative dostarlimab compared with SOC.
4. To assess the safety and tolerability of dostarlimab compared with SOC.
5. To describe the PK of dostarlimab in participants.
6. To determine the immunogenicity of dostarlimab in participants.

Conditions and MedDRA coding

Participants with Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

IPD plan description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-trsansparency/ IPD sharing access criteria: Anonymized IPD is shared with researchers whose proposals are approved by an independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted when justified, for up to 6 months. IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Is at least 18 years of age.
2. Has untreated pathologically confirmed colon adenocarcinoma.
3. Has resectable colon adenocarcinoma defined as clinically T4N0 or Stage III.
4. Has radiologically evaluable disease.
5. Has a tumor demonstrating the presence of either a dMMR status or MSI-H phenotype.
6. Participants who are known to have Lynch syndrome and have been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2) or EPCAM gene may be eligible to participate.
7. Provides a tumor tissue sample obtained at the time of or after the initial diagnosis of colon cancer.
8. Is willing to use adequate contraception.
9. Can provide a signed informed consent.
10. Has an ECOG- PS of 0 or 1.
11. Has adequate organ function.

Exclusion criteria 23

1. Has distant metastatic disease.
2. Has received any live vaccine within 30 days of enrollment.
3. Has any history of interstitial lung disease /pneumonitis and/or radiation induced enteritis. 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.
4. Has a history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the study results, interfere with their participation for the full duration of the study intervention, or indicate it is not in the best interest of the participant to participate.
5. Has a history of allogenic stem cell transplantantion or organ transplantation.
6. Has received prior medical therapy, radiation therapy or surgery for management of the current diagnosis of colon cancer.
7. Has a tumor that is causing symptomatic bowel obstruction or otherwise requires urgent/emergent surgery at the time of screening. Participants with a history of colonic obstruction are eligible after obstruction is relieved by a diverting stoma (defunctioning ileostomy or colostomy).
8. Has a tumor that is not amenable to surgery or has any other contraindication to surgery.
9. Has a known additional malignancy that progressed or required active treatment within the past 2 years.
10. Is immunocompromised.
11. Has documented presence of HBsAg at Screening or within 3 months prior to randomization.
12. Has an active autoimmune disease that has required systemic treatment in the past 2 years.
13. Has experienced any of the following with prior immunotherapy: any irAE ≥ Grade 3, immune-mediated 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.
14. Has undergone any major surgical procedure, open biopsy, or experienced significant traumatic injury within 28 days prior to enrollment.
15. Has a history of congenital long QT syndrome.
16. Has a history of or evidence of cardiac abnormalities.
17. Is receiving any other anticancer or experimental therapy.
18. Is receiving immunosuppressive medication.
19. Has received systemic corticosteroids (>10 mg daily prednisone or equivalent) within 7 days of first dose of study intervention.
20. Has a positive HCV antibody test result at Screening Visit or within 3 months prior to randomization.
21. Has a positive HCV RNA test result at Screening Visit or within 3 months prior to randomisation.
22. Is pregnant, breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 9 months after the last dose of study intervention.
23. Has any condition that would exclude the patient from chemotherapy with FOLFOX or CAPEOX.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event Free Survival (EFS) with recurrence assessed by Blinded Independent Central Review (BICR). Where an event is defined as: Disease recurrence based on radiological assessment by BICR; Disease progression precluding surgery (local assessment); Disease recurrence based on a pathological assessment of new lesions identified after surgery (local assessment); Death due to any cause; Treatment related toxicity that results in the participant not being suitable for surgery.

Secondary endpoints 6

1. Pathological response determined by local assessment.
2. OS, defined as time from randomization to death from any cause.
3. EFS with recurrence assessed by local assesment (component events are the same as primary endpoint).
4. Frequency and severity of treatment emergent AEs, SAEs, irAEs, and AEs leading to death or discontinuation of study intervention.
5. Serum concentrations and relevant PK parameters (C-EoI and Ctrough) for dostarlimab.
6. Incidence of ADA against dostarlimab.

Investigational products

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

Test 1

Comparator 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 32

Locations

14 EU/EEA countries · 97 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 375 files

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

Application history

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