A Phase 2 Trial of SCO-101 in combination with FOLFIRI for Patients with Metastatic Colorectal Cancer (mCRC) with acquired Resistance to FOLFIRI

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Scandion Oncology A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Mar 2022 → 26 Feb 2025

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Scandion Oncology A/S

External identifiers

EU CT number

2024-518877-33-00

EudraCT number

2019-003779-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Dose response

• To determine the safety and toxicity profile of SCO-101 in combination with FOLFIRI.
• Stage 1 and 3: Maximum tolerated dose (MTD) of SCO-101 in combination with FOLFIRI as evaluated by CTCAE v. 5.0.
• Stage 2: To assess the Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after 20 weeks from treatment start.

Secondary objectives 4

1. To assess the Clinical Benefit Rate (CBR), Progression Free Survival (PFS), overall survival (OS), and ORR.
2. To assess the Duration of Response (DOR) in patients with an objective response, and DOR compared to DOR of initial FOLFIRI treatment (without SCO-101).
3. To establish the PK profile of: SCO-101 in combination with FOLFIRI, and / Irinotecan, SN-38 and SN-38-glucuronide / 5-FU
4. To evaluate clinical biomarkers to predict response to SCO-101 treatment in combination with FOLFIRI. The following biomarkers will be evaluated: In all stages: Total, unconjugated and conjugated bilirubin, / UGT1A1 polymorphism

Conditions and MedDRA coding

Metastatic Colorectal Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Ability to understand and willingness to provide written informed consent before any trial-related activities.
2. Age 18 years or older.
3. Histologically verified colorectal adenocarcinoma.
4. Non-resectable mCRC in patients. A. Stage 1: with or without BRAF, RAS or known repair enzyme mutations / B. Stage 2: without known BRAF, RAS or repair enzyme mutations / C. Stage 3: with or without BRAF, RAS or repair enzyme mutations, actual status to be confirmed prior to enrollment
5. Previous treatment and documented progressive disease with irinotecan and 5-FU (including 5-FU based analogs, e.g. capecitabine) based chemotherapy regimens (with or without antiangiogenetic and EGFR inhibitory biological treatment).
6. Maximum reduction of 33% in prior dose of FOLFIRI.
7. Previous treatment with an oxaliplatin-containing treatment regimen and no indication for re-challenge with oxaliplatin. The patient can have received oxaliplatin treatment before and/or after treatment with FOLFIRI.
8. A. Stage 1 and 3 only: Evaluable disease by CT scan or MRI. / B. Stage 2 only: Measurable disease by CT scan or MRI, according to RECIST.
9. Performance status of ECOG ≤ 1.
10. Recovered to Grade 1 or less from prior surgery or acute toxicities of prior radiotherapy or treatment with cytotoxic or biologic agents.
11. ≥ 2 weeks must have elapsed since any prior surgery.
12. Adequate conditions as evidenced by the following clinical laboratory values:   • Absolute neutrophils count (ANC) ≥ 1.5 x 109/L   • Hemoglobin ≥ 6.0 mmol/L   • Platelets ≥ 100 x 109 /L   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN*   • Total serum bilirubin ≤ 1.0 ULN**   • Alkaline phosphatase ≤ 2.5 x ULN*   • Normal kidney function defined by the centers with the method usually employed locally. i.e. either creatinine (≤ 1.5 ULN) or calculated creatinine clearance or eGFR within normal limits determined according to local standards • Adequate blood clotting function as defined by the International Normalized Ratio (INR) ≤ 1.5
13. Life expectancy equal to or longer than 3 months.
14. Sexually active males and females of child-producing potential must use highly effective contraception (intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) for the study duration and at least 6 months after the last dose of study drug.
15. Signed informed consent.
16. Patients are only eligible for inclusion if no further on label treatment alternatives are available, i.e: (a) They have progressed on all available standard treatments, and/or (b) are intolerant to all remaining standard treatments, and/or (c) decline treatment with all other standard treatments, and/or (d) if the patient according to the treating physicians cannot be offered further standard treatment for their cancer disease.

Exclusion criteria 13

1. Concurrent chemotherapy, radiotherapy, or other investigational drugs during study period.
2. Malabsorption syndrome or previous surgeries with resection of the stomach or small intestine, whereby absorption of SCO-101 may be affected.  This includes patients with ileostomy.
3. Difficulty in swallowing tablets.
4. Clinical symptoms of CNS metastases requiring steroids.
5. Any active infection requiring parenteral or oral antibiotic treatment.
6. Known HIV positivity.
7. Known active hepatitis B or C.
8. Clinical significant (i.e. active) cardiovascular disease: • Stroke within ≤ 6 months prior to day 1   • Transient ischemic attach (TIA) within ≤ 6 months prior to day 1   • Myocardial infarction within ≤ 6 months prior to day 1   • Unstable angina   • New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF)   • Serious cardiac arrhythmia requiring medication
9. Mental status is not fit for clinical study or CNS disease including symptomatic epilepsy.
10. Other medications or conditions that in the Investigator’s opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results.   Other severe medical conditions, including serious heart disease, unstable diabetes, uncontrolled hypercalcemia, clinically active infections or previous organ transplants. Participation in another clinical trial with experimental medication within 30 days prior to registration.
11. Known hypersensitivity to SCO-101, irinotecan, 5-FU or structurally similar drugs (e.g. capecitabine), leucovorin and G-CSF.
12. Pregnant women or women who are breastfeeding.
13. Patients with known Dihydropyrimidine dehydrogenase (DPD) deficiency.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Safety and tolerability by assessing the number, frequency, and severity of adverse events (AEs) collected from the time of first treatment until four weeks after last administration of study treatment to evaluate safety of SCO-101 in combination with FOLFIRI determined according to CTCAE version 5.0.
2. Stage 1 and 3: Maximum tolerated dose (MTD) by evaluation of dose-limiting toxicities (DLTs) of SCO-101 in combination with FOLFIRI.
3. Stages 2: ORR defined as Complete Response (CR) and Partial Response (PR) using the RECIST v. 1.1 after 20 weeks from treatment start.

Secondary endpoints 8

1. Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first.
2. Duration of response (DOR) (from first response to progression).
3. DOR after administration of SCO-101 compared to DOR from patients’ initial FOLFIRI treatment regimen (i.e., without SCO-101).
4. Overall survival (OS) defined as time in months from the date of first study treatment to the date of death.
5. ORR defined as CR and PR using the RECIST v. 1.1 for the entire treatment period.
6. Clinical benefit rate (CBR) defined as the number of patients obtaining CR, PR, or SD ≥ 16 weeks according to RECIST v.1.1.
7. Pharmacokinetic profile of SCO-101, Irinotecan, SN-38, SN-38-glucuronide and 5-FU will be determined by means of: Time to maximum drug plasma concentration (tmax), Half-life (T½), Volume of Distribution (Vd/F), Clearance (CL/F), Area Under the plasma drug Concentration-time curve (AUC) and Maximum drug plasma concentration (Cmax).
8. Biomarker evaluation: Changes in levels of total, unconjugated and conjugated bilirubin in blood, from baseline (i.e., prior first dose of SCO-101), at each cycle, and until end of treatment; and correlation between patient tolerability and pharmacokinetic parameters for SCO-101 and FOLFIRI components. / Selected UGT1A1 polymorphism (from a pre-treatment blood sample).

Investigational products

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

Test 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Scandion Oncology A/S

Sponsor organisation

Scandion Oncology A/S

Address

Fruebjergvej 3

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Scandion Oncology A/S

Contact name

Lars Damstrup

Public contact point

Organisation

Scandion Oncology A/S

Contact name

Johnny Stilou

Third parties 6

Locations

1 EU/EEA country · 6 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 10 files

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

Application history

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