Phase 2 Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal 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

14 Mar 2023 → ongoing

Decision date (initial)

2024-03-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-509583-22-00

EudraCT number

2022-003289-18

ClinicalTrials.gov

NCT05723562

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To estimate the efficacy of dostarlimab in participants with Stage II/III (locally advanced) dMMR/MSI-H rectal cancer that has not been previously treated

Secondary objectives 4

1. To further estimate the efficacy of dostarlimab in participants with Stage II/III (locally advanced) dMMR/MSI-H rectal cancer that has not been previously treated
2. To assess the safety and tolerability of dostarlimab in participants with Stage II/III (locally advanced), dMMR/MSI-H rectal cancer that has not been previously treated
3. To describe the PK of dostarlimab in participants with Stage II/III (locally advanced), dMMR/MSI-H rectal cancer that has not been previously treated
4. To determine the immunogenicity of dostarlimab in participants with Stage II/III (locally advanced), dMMR/MSI-H rectal cancer that has not been previously treated

Conditions and MedDRA coding

Neoplasms, Rectal

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Is at least 18 years of age (or the local legal age of consent) at the time of signing the ICF
2. Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+) locally advanced rectal adenocarcinoma
3. Has radiologically and endoscopically evaluable disease
4. Has an archival FFPE tissue sample that must be available and submitted to the central reference laboratory for testing at Screening
5. Has an ECOG performance status of 0 or 1
6. Has adequate organ function
7. Has a tumor demonstrating the presence of either dMMR status or MSI-H phenotype

Exclusion criteria 8

1. Has distant metastatic disease
2. Has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer
3. Has a tumor that, in the investigator's judgment, is causing symptomatic bowel obstruction or otherwise requires urgent/emergent local intervention
4. Has a known additional malignancy that progressed or required active treatment within the past 2 years (Exceptions include adequately treated superficial skin cancers, superficial bladder cancers, and other in situ cancers)
5. Is immunocompromised in the opinion of the investigator
6. Has an active autoimmune disease that has required systemic treatment in the past 2 years
7. Is receiving immunosuppressive medication ; Has received systemic corticosteroids
8. Has received or plans to receive an organ or stem cell transplant that uses donor stem cells (allogeneic stem cell transplant).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. cCR12 as assessed by ICR, defined as maintenance of cCR for 12 months. The 12-month period starts from the first disease assessment after last dose of study intervention that demonstrates cCR by ICR.

Secondary endpoints 3

1. cCR24 as assessed by ICR, defined as maintenance of cCR for 24 months. The 24-month period starts from the first disease assessment after last dose of study intervention that demonstrates cCR by ICR.
2. cCR36 as assessed by ICR, defined as maintenance of cCR for 36 months. The 36-month period starts from the first disease assessment after last dose of study intervention that demonstrates cCR by ICR
3. EFS3 as assessed by investigator assessment, defined as remaining alive and free of 1) disease progression precluding surgery, 2) local recurrence, and 3) distant recurrence, as assessed by investigator at 3 years from the first dose of study intervention.

Investigational products

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

Test 1

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 10

Locations

5 EU/EEA countries · 20 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 84 files

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

Application history

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