A Phase II clinical trial comparing the efficacy of RO7198457 versus watchful waiting in patients with ctDNA positive, resected Stage II (high risk) and Stage III colorectal cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Feb 2021 → ongoing

Decision date (initial)

2024-03-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509516-28-00

EudraCT number

2020-000451-12

WHO UTN

U1111-1250-5294

ClinicalTrials.gov

NCT04486378

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacodynamic, Safety

Demonstrate superiority of RO7198457 compared to “watchful waiting” in terms of DFS in chemotherapy pretreated patients.

Secondary objectives 3

1. To assess the efficacy of RO7198457 compared to “watchful waiting” in terms of relapse-free survival (RFS), time to recurrence (TTR), time to treatment failure (TTF), and overall survival (OS).
2. To assess anti-tumor efficacy.
3. To assess the safety and tolerability of RO7198457.

Conditions and MedDRA coding

Stage II/Stage III rectal cancer or Stage II (high risk)/Stage III colon cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Patients must be a man or woman of at least 18 years of age.
2. Patients must have given informed consent indicating that they understand the purpose of and procedures required for the trial and are willing to participate in the trial.
3. Patients must have Stage II/Stage III rectal cancer or Stage II (high risk)/Stage III colon cancer per AJCC 2017 that has been surgically totally resected (R0 confirmed by pathology report).
4. Patients must have detectable ctDNA prior to start of adjuvant chemotherapy (AdCTx) (except for the Biomarker Cohort).
5. Patients must have an ECOG Performance Status of 0-1.
6. Patients must have organ and bone marrow function, in line with all of the following: ANC ≥1.5x 10E9/L (1500/mL) without granulocyte colony-stimulating factor support. Lymphocyte count ≥0.5x 10E9/L (500/µL). Platelet count ≥100x 10E9/L (100,000/µL) without transfusion. Hemoglobin ≥90 g/L (9 g/dL) patients may be transfused to meet this criterion. For patients not receiving therapeutic anticoagulation: INR or aPTT ≤1.5x upper limit of normal (ULN). For patients receiving therapeutic anticoagulation: stable anticoagulant regimen. GFR ≥30 mL/min. AST, ALT, and ALP ≤2.5x ULN. Bilirubin ≤1.5x ULN with the following exception: for patients with known Gilbert disease: bilirubin ≤3x ULN.
7. Women must be either not of childbearing potential or if of childbearing potential, be practicing a highly effective method of birth control during the trial and for 28 d after receiving the last dose of RO7198457.
8. Women of childbearing potential must have a negative serum pregnancy test.
9. Men who are sexually active with women of childbearing potential and who have not had a vasectomy must agree to use a highly effective method of birth control during the trial and for 28 days after receiving the last dose of IMP.
10. Patients must be willing and able to adhere to the restrictions specified in this protocol.
11. Adequate tumor material in formalin-fixed paraffin embedded (FFPE) blocks or as sectioned tissue (only upon approval by sponsor) must be available. Resections are preferred. The specimens should be submitted along with an associated pathology report.
12. At least 5 tumor neoantigens identified in the provided tumor sample.
13. The patient has started a standard of care AdCTx within 8 weeks post-surgery and has completed at least 3 months of treatment of a 3 or a 6-month course of chemotherapy (including rest days).

Exclusion criteria 16

1. Patients with uncontrolled intercurrent illness, including any of but not limited to: Severe infections within 4 weeks prior to the first dose of RO7198457 including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. Symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia. Respiratory failure. Recent infections not meeting the criteria for severe infections, including the following: Signs or symptoms of infection within 2 weeks prior to the first dose of RO7198457. Received oral or IV antibiotics within 2 weeks prior to the first dose of RO7198457. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
2. Diagnosed MSI high tumors.
3. Prior therapy with any of the following: Neo-adjuvant (radio)chemotherapy prior to surgery. Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of trial treatment or anticipation of need for systemic immunosuppressive medication during trial treatment, with the exception of low dose steroids defined as 10 mg oral prednisone (or equivalent). Current or recent treatment with another investigational drug.
4. Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
5. Patients who developed metastatic disease during screening/receiving standard of care treatment (not applicable for Exploratory Cohort).
6. Patients with known past or current malignancy other than inclusion diagnosis, except for: - Cervical carcinoma of Stage 1B or less. - Non-invasive basal cell or squamous cell skin carcinoma. - Non-invasive, superficial bladder cancer. - Prostate cancer with a current PSA level <0.1 ng/mL. - Any curable cancer with a complete response (CR) of >2 years duration.
7. Patients with known allergies, hypersensitivity, or intolerance to RO7198457 or its excipients.
8. Patients are currently enrolled in an ongoing clinical trial or trial that could interfere with the protocol-specified assessments.
9. Patients with any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments.
10. Patients who had major surgery within 4 weeks before screening, or will not have fully recovered from surgery, or have surgery planned during the time the patient are expected to participate in the trial.
11. Patients with positive serology for hepatitis B based on a test for antibodies to hepatitis B core antigens (anti-HBc) and a negative test for antibodies to hepatitis B surface antigens (anti-HBs).
12. Active Hepatitis C virus (HCV) infection; patients who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.
13. Patients who have a history of human immunodeficiency virus (HIV) antibody positivity, or tests positive for HIV at screening.
14. Patients who were enrolled in this trial before.
15. Patients who are breastfeeding at screening visits 2 or 3, or who plan to breastfeed during the trial, starting after the start of treatment with RO7198457 and continuously until at least 90 d after receiving the last dose of RO7198457.
16. Patients who have had prior splenectomy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free survival (DFS) defined as the time from randomization to occurrence of any of the following events, whichever occurs first: Locoregional recurrence or distant metastases as determined by an independent central radiology assessment. Occurrence of second primary (same or other) cancer as determined by an independent central radiology assessment. Death from any cause. Loss to follow-up is censored.

Secondary endpoints 6

1. Relapse-free survival (RFS) is defined as the time from randomization to occurrence of any of the following events, whichever occurs first: Locoregional recurrence or distant metastases as determined by the investigator. Death from any cause. Occurrence of second primary (same or other) cancer as determined by the investigator is ignored. Loss to follow-up is censored.
2. Time to recurrence (TTR) is defined as the time from randomization to occurrence of any of the following events (i.e., events related to the same cancer), whichever occurs first: Locoregional recurrence or distant metastases as determined by the investigator. Death from same cancer. Occurrence of second primary (same or other) cancer as determined by the investigator is ignored. Loss to follow-up and deaths from other cancer, non-cancer-related deaths, treatment-related deaths are censored.
3. Time to treatment failure (TTF) is defined as the time from randomization to occurrence of any of the following events, whichever occurs first: Locoregional recurrence or distant metastases as determined by the investigator. Occurrence of second primary (same or other) cancer as determined by the investigator. Death from any cause except non-cancer-related death. Loss to follow-up and non–cancer-related deaths are censored.
4. Overall survival (OS) defined as the time from randomization to death from any cause. Change of ctDNA status (approx. every 3 months).
5. Occurrence of treatment-emergent adverse events (TEAEs), including Grade 3+, serious, fatal TEAEs by relationship. Occurrence of dose reduction and discontinuation of RO7198457 due to a TEAE.
6. Change of ctDNA status (approx. every 3 months).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech SE

Sponsor organisation

BioNTech SE

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Third parties 8

Locations

4 EU/EEA countries · 61 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 119 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