Phase II Clinical Trial of KORTUC (KRC-01) Combined with Radiotherapy for Locally Advanced Rectal Cancer: Towards a New Organ Preservation Approach (K-BOOST)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Gustave Roussy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

KORTUC INC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the clinical complete response (cCR) rate after completion of the treatment combining radiotherapy and intratumoral KRC-01 injections in patients with locally advanced rectal cancer. (we select cCR over pCR because some patients might never be operated on in case of major responses).

Secondary objectives 10

1. To evaluate the safety and tolerability of the treatment (incidence and severity of KRC-01-related adverse events).
2. To assess the pathological complete response (pCR) rate (only for those undergoing TME).
3. To estimate progression-free survival and overall survival at 1 and 2 years.
4. To assess the impact of treatment on quality of life (QLQ-C30 and EQ-5D-5L questionnaires)
5. Identify of predictive and prognostic biomarkers of treatment response (circulating and tumor-derived).
6. Correlate between radiological response (RECIST) and metabolic response (PET imaging).
7. Characterize systemic and intratumoral immune modulation induced by KRC-01 and chemotherapy (flow cytometry, immunohistochemistry, single-cell RNAseq).
8. Evaluate of circulating biomarkers (e.g., ctDNA, cytokines) and correlation with clinical response.
9. Analyze of gut microbiome modifications during treatment and association with therapeutic outcomes.
10. To longitudinal assess of patient-reported quality of life and symptom burden throughout treatment and follow-up.

Conditions and MedDRA coding

Locally advanced high‑risk stage III rectal adenocarcinoma (non‑metastatic)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. 1. Males and females ≥ 18 years of age
2. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
3. 3. Histopathologically confirmed locally advanced rectal adenocarcinoma, stage III (high risk)
4. 4. No evidence of metastatic disease on computed tomography (chest and abdomen), including resectable metastases. (M0, and no oligometastases)
5. 5. At least one of the following criteria: cT4a, cT4b, presence of extramural invasion (EMVI+), cN2, involvement of the mesorectal fascia (MFI+), involvement of lateral lymph nodes (lat LN+)
6. 6. Adenocarcinoma located with a lower border less than 15 cm from the anal margin
7. 7. Primary resection without chemoradiotherapy is unlikely to achieve clear margins.
8. 8. Tumor lesion must be mesurable by endoscopic visual assessment
9. 9. Target tumor is accessible for intratumoral injections.
10. 10. Intention to undergo treatment including 5 Fu based chemoradiotherapy and CAPOX (6 cycles) or FOLFOX (9 cycles)
11. 11. Life expectancy > 6 months
12. 12. Acceptable organ functions, as evidenced by the laboratory data described in the protocol
13. 13. Women of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days prior to the administration of the first study treatment and/or urine pregnancy 12 hours prior to the administration of the first study treatment.
14. 14. Patients who either do not consent to a tumor biopsy or do not have accessible lesions will not be eligible.
15. 15. Patients should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
16. 16. Patient should be able and willing to comply with study visits and procedures as per protocol.
17. 17. Patient must be affiliated to a social security system or beneficiary of the same.

Exclusion criteria 19

1. 1. Patients not deemed fit for radiotherapy or preexisting condition which would deter radiotherapy, e.g., fistulas, severe ulcerative colitis (including subjects currently taking sulphasalazine), active Crohn’s disease, prior adhesions.
2. 14. Concomitant medications/comorbidities that may prevent the patient from receiving study treatments
3. 15. Contraindication to fluoropyrimidines or oxaliplatin and capecitabin
4. 16. Yellow fever vaccine and live attenuated vaccines are contraindicated due to the risk of severe vaccine-induced infection. Note: The currently authorized COVID-19 vaccines are not live vaccines and therefore can be safely administered.
5. 17. Known history of human immunodeficiency virus (HIV) infection or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
6. 18. Pregnant or breastfeeding women or intending to become pregnant during the clinical investigation.
7. 19. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
8. 3. Any Previous radiotherapy in the pelvic region.
9. 4. contraindications to MRI (e.g., subjects with pacemakers, claustrophobia, excessive weight, etc.).
10. 5. Participation in another clinical study with an investigational product during the last 3 months.
11. 6. Prior rectal surgery.
12. 7. Prior investigational treatment for rectal cancer.
13. 9. High medical risk because of systemic diseases (e.g., uncontrolled infections, uncontrolled diabetes) in addition to the qualifying disease under study.
14. 12. Peripheral sensory neuropathy grade ≥2 (for the future administration of oxaliplatin)
15. 13. Dihydropyrimidine deshydrogenase (DPD) deficiency. DPD status must be assessed prior to inclusion, and uracilemia testing is mandatory before initiation of fluorouracil-based treatment. Patients with unknown DPD status are not eligible.
16. 2. Patients with hypokalemia below the lower limit of normal, hypomagnesemia, hypocalcemia, or QT/QTc interval >450 msec in males or >470 msec in females at inclusion are not eligible.
17. 8. Patients with known high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) tumors are not eligible, as these patients may benefit from standard-of-care immunotherapy.
18. 10. Patients receiving therapeutic anticoagulation are not eligible. Prophylactic anticoagulation at low dose (e.g., thromboprophylaxis) may be allowed at the investigator’s discretion, provided that the bleeding risk is considered minimal.
19. 11. Patients receiving concomitant treatment with brivudine or who have received brivudine within the previous 4 weeks.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical Complete Response (cCR) rate at week 24

Secondary endpoints 11

1. OS defined as the time from inclusion until death from any cause. Patients who are alive at last follow-up news will be censored at this date.
2. PFS defined as the time from inclusion until first documentation of progression or death, whichever occurs first.
3. The percentage of patient with pCR defined as the complete absence of viable tumor cells, or the major pathologic response (MPR) defined as less than 10% of surviving tumor cells in in the surgical specimen.
4. The incidence of adverse events (AEs) NCI-CTCAE v6.0
5. Scores from EORTC QLQ-C30 and EQ-5D-5L questionnaires at baseline, Week 6 and Week 24.
6. Identification of predictive and prognostic biomarkers of treatment response (circulating and tumor-derived).
7. Correlation between radiological response (RECIST) and metabolic response (PET imaging).
8. Characterization of systemic and intratumoral immune modulation induced by KRC-01 and chemotherapy (flow cytometry, immunohistochemistry, single-cell RNAseq)
9. Evaluation of circulating biomarkers (e.g., ctDNA, cytokines) and correlation with clinical response
10. Analysis of gut microbiome modifications during treatment and association with therapeutic outcomes.
11. Longitudinal assessment of patient-reported quality of life and symptom burden throughout treatment and follow-up.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Gustave Roussy

Sponsor organisation

Institut Gustave Roussy

Address

114 Rue Edouard Vaillant

City

Villejuif

Postcode

94800

Country

France

Scientific contact point

Organisation

Institut Gustave Roussy

Contact name

Bureau projet Promotion- DRC -Regulatory Affairs Officer

Public contact point

Organisation

Institut Gustave Roussy

Contact name

Bureau projet Promotion- DRC -Regulatory Affairs Officer

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

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

Application history

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