A First-In-Human, phase I/IIa, open-label trial assessing safety, tolerability, and feasibility of repeated administrations of a novel autologous tumor-infiltrating lymphocyte-based immunotherapy in patients with metastatic colorectal or prostate cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CuraCell Holding AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Digestive System Diseases [C06]

Trial duration

13 Nov 2025 → ongoing

Decision date (initial)

2025-07-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of the trial is to evaluate the safety, tolerability, and feasibility of repeated administrations of the novel ATIMP, TIL (CC-38), in patients with locally advanced or metastatic prostate cancer or metastatic colorectal cancer.

Secondary objectives 1

1. The secondary objectives of the trial are to evaluate the efficacy of repeated administrations of the novel ATIMP, TIL (CC-38), in patients with locally advanced / metastatic prostate cancer or metastatic colorectal cancer.

Conditions and MedDRA coding

Patients with locally advanced or metastatic prostate cancer (PCa) or metastatic colorectal cancer. Participants should have progressive disease.

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Patient (female or male) has signed informed consent according to ICH/GCP and national/local regulations prior to any trial-specific procedure.
2. Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Patient has a minimum life expectancy of 6 months in the opinion of the investigator from the time of consent date.
4. Patient has adequate bone marrow, hepatic and renal function in the opinion of the investigator: a) Hemoglobin ≥ 9.0 g/dL, b) Absolute neutrophil count (ANC) ≥ 1.0 x 109 /L, c) Platelets ≥ 80 x 109 /L, d) Calculated creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula), e) Serum bilirubin ≤ 1.5 x ULN (or ≤ 2.5 x ULN in the presence of documented Gilbert‘s Syndrome [unconjugated hyperbilirubinemia] or liver metastases), f) AST/ ALT and alkaline phosphatase ≤ 2.5 x ULN (or ≤ 5 times ULN in the presence of bone and/or liver metastases), ALP ≤ 2.5 x ULN, g) International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ ULN + 4 seconds.
5. Female patients must be post-menopausal or use contraceptive methods with a failure rate of < 1% (see section 5.2.6) until 12 months [redacted information] or 6 months after last administration of CC-38, whatever is later, to prevent pregnancy. Male patients with fertile female partners must be willing to use condoms with spermicide, and the fertile partner must use contraceptive methods with a failure rate of < 1% for the above given time period to prevent pregnancy. Male patients must also refrain from donating sperm for the same time period.
6. Successful tumor tissue sampling by surgery, including presence of TILs in the tumor tissue in the pathological evaluation (refer to section 4.4.2).
7. Successful TIL expansion defined as obtaining the final CC-38 drug product of ...[redacted information].
8. Patient is 18 years or older at the time of signing the informed consent form.
9. 3. Patient weight above >50 kg.
10. Patient must live in an area where a hospital for care can be reached within a maximum of 50 km.
11. Patient has histological or cytological confirmation of: • colorectal cancer, which is stage IV (any T/ any N/ M1), not amenable to curative surgery, OR • prostate cancer, which is stage III locally advanced, not amenable to curative surgery (T3-4 / N0 / M0 or any T / N1 / M0), or stage IV metastatic (any T / any N / M1).
12. Patient has received all lines of therapy that • are considered SOC for the patient’s indication according to applicable European/national professional society medical guidelines and local medical practice at time of enrollment • are available via the national health insurance system and the patient is considered eligible for but led to insufficient response or were medically not justified or refused by the patient.
13. Patient has confirmed disease progression by radiologic imaging from the previous line of therapy.
14. Patient has sufficient amount of previously not irradiated tumor tissue in adequate quality ([redacted information]) for TIL harvest and expansion, i.e., either: • primary or metastatic lesion has been selected for surgery (e.g., to reduce tumor burden, pain relief), OR • patient has consented to surgery for the purpose of tissue harvesting for TIL expansion and is considered suitable to undergo surgery for this purpose. NOTE: Patients with a non-justifiable anesthesiologic and/or surgical risk, as determined by the investigator, will be excluded.
15. Patient has at least one measurable or assessable lesion according to RECIST 1.1 remaining after tumor resection for CC-38 manufacturing has been performed.

Exclusion criteria 27

1. Patient has any of the following condition: a) congestive heart failure NYHA class III or IV, b) myocardial infarction or coronary artery bypass graft within 6 months prior to enrollment, c) history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration, d) history of severe non-ischemic cardiomyopathy, e) uncontrolled blood pressure as defined as systolic > 160 mmHg, diastolic > 100 mmHg within 3 months prior to enrollment, f) left ventricular ejection fraction (LVEF) < 45% as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan, g) any other clinically significant cardiovascular events such as unstable angina, angioplasty, stroke, or transient ischemic attack (TIA) within less than 6 months before enrolment, h) other conditions that the treating physicians believe may endanger the health of the patients by their participation in this clinical trial.
2. Patient has any of the following pulmonary conditions: a) forced expiratory volume in 1 second (FEV1) < 60%, b) active obstructive chronic pulmonary disease, c) oxygen dependence as defined by a blood oxygen saturation that can only be maintained above 92% by oxygen inhalation (finger oxygen detection method), d) other pulmonary conditions that increase the anesthesiologic risk.
3. Patient has a current or history of central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression.
4. Patient has ulcers in the upper gastrointestinal (GI) tract, untreated or incompletely treated esophageal varices with high risk of bleeding in the investigator’s discretion.
5. Patients who require therapeutic anticoagulant therapy or are otherwise at increased risk of bleeding events.
6. Patient has any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of trial results in the opinion of the investigator.
7. Patient has any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] or acquired immune deficiency syndrome [AIDS]).
8. Patient has active or history of autoimmune or inflammatory disorders. Note: Patients may be eligible if they have been assessed in discussion between Principal Investigator, Chief Medical Officer and Senior Medical Consultant as not posing an increased risk to the patient.
9. Patient receiving immunosuppressive concomitant medications (≥ 10 mg prednisone daily or other equivalent). Steroid medications are allowed if they are used as substitution or are administrated topically or as inhalations.
10. [redacted information]
11. Patient has received an organ and/or allogenic stem cell transplant.
12. Patient has known acute or chronic infection with hepatitis B or C virus.
13. Patient has known Human Immunodeficiency Virus HIV infection (seropositive for HIV antibody).
14. Patient has known infection with syphilis.
15. Patient has known bone-marrow aplasia.
16. Patient has known chronical urinary tract infection and/or acute urothelial toxicity from previous cytotoxic chemotherapy, radiation therapy, or urinary flow obstructions.
17. Female patient, who is pregnant or breast-feeding, or plan to become pregnant within 12 months after cyclophosphamide or 6 months after last dose of CC-38, whichever last. Women of childbearing potential must have a negative pregnancy test at screening and before every CC-38 administration.
18. Patient is unable to comply with trial procedures, restrictions, or requirements.
19. Patient received last previous systemic cancer treatment (including anti-testosterone treatment) within less than 4 weeks prior enrollment. Note: Bridging therapies (specified in trial design [section 2 – subsection: initial screening and TIL harvesting]) after TIL harvesting and before CC-38 administration are permitted after consultation between Principal Investigator, Chief Medical Officer, and Senior Medical Consultant.
20. Patient received last palliative radiotherapy within less than 4 weeks prior enrollment – where RECIST 1.1 evaluable metastases are within the radiation area.
21. Patient received minor surgery within less than 3 weeks prior enrollment.
22. Patient with AEs from previous treatment that have not recovered to Common Terminology Criteria for Adverse Event (CTCAE) v5.0 ≤ grade 1, [redacted information] Note: Clinically insignificant grade 2 AEs may be allowable if discussed between and approved by Principal Investigator, Chief Medical Officer, and Senior Medical Consultant.
23. Patient participates in any other interventional clinical trial or has been treated with any investigational research products within 4 weeks prior to the initiation of screening.
24. Patient has bone metastasis only.
25. Patient has known hypersensitivity to any component of the trial regimen.
26. For colorectal cancer: Patient has been diagnosed with histologically or cytologically proven BRAF-V600 positive CRC.
27. Patient has any further contraindication to the IMP pembrolizumab or any of the auxiliary medicinal products (i.e., IL-2, cyclophosphamide, uromitexan) as per current EU SmPCs to the respective product.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment emergent adverse events (TEAE) and the occurrence of severity grade 3 or higher adverse events according to NCI CTCAE v5.0; Proportion of patients receiving at least two TIL administrations without TEAEs preventing TIL administration

Secondary endpoints 6

1. Measurable objective response rate, defined as proportion of patients with complete [CR] or partial response [PR] as best response to treatment within the first 6 months after start of CC-38 administration, as assessed by the Investigator according to RECIST 1.1 and iRECIST (ORR/ iORR)
2. Progression-free survival, defined as the time from start of treatment to time of disease progression, as assessed by the Investigator according to RECIST 1.1 and iRECIST (PFS/ iPFS), or death from any cause, whichever comes first
3. Time to tumor progression, defined as time from start of treatment to disease progression as assessed by the Investigator according to RECIST 1.1 and iRECIST (TTP/ iTTP)
4. Overall survival (OS), defined as time from start of treatment to time of death from any cause
5. For prostate cancer cohort: Patient individual changes in prostate-specific antigen (PSA) levels from baseline until 6 months after start of treatment; in addition, changes in tumor spread will be assessed by PSMA PET-CT at baseline and after third CC-38 administration
6. For colorectal cancer cohort: Patient individual changes in biomarkers (including elevated tumor markers, i.e., carcinoembryonic antigen [CEA] and cancer antigen 19-9 [CA-19-9] levels) from baseline until 6 months after start of treatment

Investigational products

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

Test 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CuraCell Holding AB

Sponsor organisation

CuraCell Holding AB

Address

Nanna Svartz Vag 4

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

CuraCell Holding AB

Contact name

Torbjörn Ström

Public contact point

Organisation

CuraCell Holding AB

Contact name

Torbjörn Ström

Third parties 3

Locations

1 EU/EEA country · 1 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 12 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