Atezolizumab in Patients With MSI-h/MMR-D Stage II High Risk and Stage III Colorectal Cancer Ineligible for Oxaliplatin

NCT05118724 | Active Not Recruiting Phase 2

• 1 other identifier: AIO-KRK-0220
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that atezolizumab will improve the prognosis of patients with stage III dMMR CRC ineligible for or refusing oxaliplatin-based adjuvant chemotherapy compared to SOC and that these could therefore be promising therapeutic options.

Conditions

Colorectal Cancer

Keywords

MSI-high; MMR-deficient; Stage III Colorectal Cancer; stage II high risk Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  DFS-rate

  at 3 years

Secondary Outcomes (2)

• Disease-free Survival (DFS)

  at 1, 2, 5 years

• Overall Survival (OS)

  at 1, 2, 3, 5 years

Study Arms (2)

Atezolizumab

EXPERIMENTAL

Atezolizumab 840mg i.v. (q2w) for a total of 12 cycles (24 doses)

Drug: Atezolizumab

IMM-101 plus atezolizumab

EXPERIMENTAL

One initial dose of IMM-101 intradermally at 1.0 mg 14 ±2 days before start of atezolizumab treatment (same as Arm A)

Drug: Atezolizumab; Drug: IMM-101

Interventions

Atezolizumab DRUG

Atezolizumab 840mg i.v., on Day 1 and Day 15 (q2w) of every 28-day treatment cycle for a total of 12 cycles (24 doses)

Also known as: Tecentriq

Atezolizumab; IMM-101 plus atezolizumab

IMM-101 DRUG

Suspension of Heat-Killed Whole Cell Mycobacterium obuense (NCTC 13365) in Borate Buffered Saline for Intradermal Injection

IMM-101 plus atezolizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Male or female ≥ 18 years of age
• Histologically confirmed adenocarcinoma of the colon or rectum
• For the main study: Pathological Stage III disease For the perioperative sub-study: Clinical stage III disease
• For the main study: R0-resected primary tumor For the perioperative sub-study: Resectable primary tumor; R0 resection anticipated (R1-resected patients can remain on study.)
• Tumor is MSI-high (MSI-H) or MMR-deficient (dMMR) For the main study: assessed from biopsy or from resected tumor tissue For the perioperative sub-study: assessed from biopsy
• ECOG status 0 - 2
• Ineligible for oxaliplatin-based adjuvant chemotherapy or patient's refusal of oxaliplatin-based adjuvant chemotherapy. Oxaliplatin ineligibility criteria are:
• Age ≥70
• Peripheral sensory neuropathy \> grade 1
• QT interval prolongation or co-medication with drugs known to prolong the QT interval
• Renal impairment (glomerular filtration rate \<60ml per min)
• Suboptimal controlled diabetes mellitus (HbA1C\>6,5%) with the risk of aggravation upon corticoid premedication for oxaliplatin based chemotherapy
• Adequate blood count, liver enzymes, and renal function - re-testing can be undergone once in case of initial results near cutoff
• White blood cell count ≥ 3.5 x 106/mL

You may not qualify if:

• Severe infection within 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, known active pulmonary disease with hypoxia, or severe pneumonia or any active infection (bacterial, viral or fungal) requiring systemic therapy within 4 weeks prior to registration. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Patients with positive test result for SARS-CoV2 should be managed as per local institutional guidelines.
• For the main study: Distant metastases or residual disease For the perioperative sub-study: Distant metastases or macroscopic residual disease (R2 resection status)
• Neoadjuvant radiotherapy or radio-chemotherapy (enrollment of rectal cancer patients without prior radio- or radio-chemotherapy is allowed); prior neoadjuvant radio-chemotherapy (RCT) or radiotherapy (RT) for rectal cancer is allowed if \>5 years and secondary colorectal cancer
• Prior adjuvant chemotherapy for colorectal cancer; allowed if \>5 years and secondary colorectal cancer
• Prior treatment with atezolizumab or any other checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti- CTLA-4)
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to treatment start, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible. Inhaled corticosteroids for chronic obstructive pulmonary disease or bronchial asthma, supplemental mineralo-corticosteroids or low-dose corticosteroids for adrenal-cortical insufficiency are allowed
• Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment.
• History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins.
• Known hypersensitivity to CHO cell products or any component of the atezolizumab formulation.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), druginduced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. If any of these lung diseases is suspected based on the patient's history or the integrated evaluation of clinical and radiological records, an additional spirometry should be conducted.
• Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening followed by a negative HBV DNA test, are eligible for the study. The HBV DNA test will be performed only for patients who have a positive total HBcAb test. Patients are also eligible if HBV DNA \< 500 IU/mL obtained within 28 days prior to initiation of study treatment, AND anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study.
• Anti-viral therapy against HCV during the trial (but allowed prior to trial)
• Positive human immunodeficiency virus (HIV) test. As an exception, known HIV+ patients may be included if they have:
• A stable regimen of highly active anti-retroviral therapy (HAART)

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Roche Pharma AG: collaborator
• Immodulon Therapeutics Ltd: collaborator

Study Sites (1)

Westdeutsches Tumorzentrum

Essen, 45147, Germany

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Turcot syndrome

Interventions

atezolizumab; IMM-101

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Stefan Kasper-Virchow, MD

  Universitätsklinikum Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: November 12, 2021
• Study Start: December 10, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)