A Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer

Neoplasms, Rectal Clinical Trial

— AZUR-1  

Official title:

A Phase 2, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05723562
• Other study ID #: 219369
• Secondary ID: 2022-003289-18
• Status: Recruiting
• Phase: Phase 2
• Start date: April 3, 2023
• Est. completion date: October 11, 2029

Study information

• Verified date: February 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate dostarlimab monotherapy in participants with locally advanced Mismatch-repair deficient (dMMR)/Microsatellite instability-high (MSI-H) rectal cancer who have received no prior treatment. Participants who achieve complete clinical response (cCR) following dostarlimab treatment will undergo non-operative management (NOM), including close surveillance for recurrent disease. The goal of the study is to determine if Dostarlimab therapy alone is an effective treatment that can allow participants to avoid chemotherapy, radiation, and surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 11, 2029
• Est. primary completion date: November 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+), locally advanced rectal cancer
• Participant has radiologically and endoscopically evaluable disease.
• Participant has a tumor which can be categorized as dMMR or MSI-H by local or central assessment

Exclusion Criteria:

• Participant has distant metastatic disease.
• Participant has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer.
• Participant has any history of interstitial lung disease or pneumonitis
• Participant has experienced any of the following with prior immunotherapy: any irAE of Grade =3, 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 (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS syndrome), or myocarditis of any grade. Non clinically significant laboratory abnormalities are not exclusionary.
• Participant 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.
• Participant has an 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.
• Participant has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or has known allergies to dostarlimab or its excipients.
• Has received or plans to receive an organ or stem cell transplant that uses donor stem cells (allogeneic stem cell transplant).

Related Conditions & MeSH terms

• Neoplasms, Rectal
• Rectal Neoplasms

Intervention

Biological:
• Dostarlimab
Dostarlimab will be administered.

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Montréal	Quebec
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
France	GSK Investigational Site	Besançon cedex
France	GSK Investigational Site	Marseille Cedex 9
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Pessac cedex
France	GSK Investigational Site	Rennes
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Muenchen	Bayern
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Pisa	Toscana
Italy	GSK Investigational Site	Roma	Lazio
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Netherlands	GSK Investigational Site	Utrecht
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Valencia
United Kingdom	GSK Investigational Site	Leeds
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Sutton	Surrey
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Amarillo	Texas
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Greenville	North Carolina
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Sustained Complete Clinical Response for 12 Months (cCR12) as assessed by Independent Central Review (ICR)	cCR12 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 12 months following their post-intervention disease assessment (PIDA)	18 Months
Secondary	Number of Participants with Sustained Complete Clinical Response for 24 Months (cCR24) as assessed by ICR	cCR24 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 24 months following their post-Intervention disease assessment (PIDA)	30 Months
Secondary	Number of Participants with Sustained Complete Clinical Response for 36 Months (cCR36) as assessed by ICR	cCR36 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 36 months following their post-Intervention disease assessment (PIDA)	42 Months
Secondary	Number of Participants with Event Free Survival at 3 years (EFS3) as assessed by Investigator	EFS3 is defined as participants who remained alive and free of disease progression precluding surgery, local recurrence, and distant recurrence at 3 years as assessed by Investigator	3 years
Secondary	Event Free Survival (EFS) as assessed by Investigator	EFS is defined as time from the date of first dose of study intervention to any of the following events: progression of disease that precludes surgery, local recurrence, distant recurrence (all as assessed by the investigator), or death due to any cause	Up to 74 months
Secondary	Number of Participants with cCR12 as assessed by Investigator	cCR12 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 12 months following their post-intervention disease assessment (PIDA)	18 Months
Secondary	Number of Participants with cCR24 as assessed by Investigator	cCR24 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 24 months following their post-intervention disease assessment (PIDA)	30 Months
Secondary	Number of Participants with cCR36 as assessed by Investigator	cCR36 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 36 months following their post-intervention disease assessment (PIDA)	42 Months
Secondary	Objective Response Rate (ORR) assessed by ICR	ORR is defined as number of participants achieving a partial response (PR), near complete response (nCR) or complete clinical response (cCR) at PIDA or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or incomplete clinical response (iCR) (PIDA 2) as assessed by ICR	Up to 33 Weeks
Secondary	Objective Response Rate (ORR) as assessed by Investigator	ORR by Investigator, defined as achieving a PR, nCR, or cCR at PIDA or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or iCR	Up to 33 Weeks
Secondary	Organ Preservation Rate	Organ Preservation Rate defined as not undergoing Total Mesorectal Excision (TME), either as primary management or for local recurrence, or who did not have a permanent colostomy created, at any time up to 3 years	3 years
Secondary	Disease-Specific Survival (DSS)	DSS is defined as time from the date of first dose of study intervention to death due to disease	Up to 74 months
Secondary	Disease-Specific Response at 5 years (DSS5)	DSS5 is defined as the number of participants not dying due to disease under study at 5 years from the first dose of study intervention	Up to 5 years
Secondary	Overall Survival (OS)	OS is defined as time from first dose of study intervention to death from any cause	Up to 74 months
Secondary	Overall Survival at 5 years (OS5)	OS is defined as number of participants as being alive at 5 years from first dose of study intervention	Up to 5 years
Secondary	Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Immune related Adverse Events (irAEs) based on Severity		Up to 74 months
Secondary	Number of Participants with discontinuation of study intervention		Up to 24 weeks
Secondary	Serum concentration of Dostarlimab		Up to 37 weeks
Secondary	Concentration at the end of infusion (C-EOI) of Dostarlimab		Up to 37 weeks
Secondary	Trough Concentration (C-trough) of Dostarlimab		Up to 37 weeks
Secondary	Number of Participants with Anti-Drug Antibodies against Dostarlimab		Up to 37 weeks