PEMBROLIZUMAB for Metastatic colorectal cancer|Locally advanced or metastatic prostate cancer

Inclusion criteria

• {"criterion_text":"- Patient (female or male) has signed informed consent according to ICH/GCP and national/local regulations prior to any trial-specific procedure.\n- Patient must live in an area where a hospital for care can be reached within a maximum of 50 km.\n- Patient has histological or cytological confirmation of: •\tcolorectal cancer, which is stage IV (any T/ any N/ M1), not amenable to curative surgery, OR •\tprostate 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).\n- Patient has received all lines of therapy that •\tare considered SOC for the patient’s indication according to applicable European/national professional society medical guidelines and local medical practice at time of enrollment •\tare 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.\n- Patient has confirmed disease progression by radiologic imaging from the previous line of therapy.\n- Patient has sufficient amount of previously not irradiated tumor tissue in adequate quality ([redacted information]) for TIL harvest and expansion, i.e., either: •\tprimary or metastatic lesion has been selected for surgery (e.g., to reduce tumor burden, pain relief), OR •\tpatient 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.\n- 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.\n- Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n- Patient has a minimum life expectancy of 6 months in the opinion of the investigator from the time of consent date.\n- Patient has adequate bone marrow, hepatic and renal function in the opinion of the investigator: a)\tHemoglobin ≥ 9.0 g/dL, b)\tAbsolute neutrophil count (ANC) ≥ 1.0 x 109 /L, c)\tPlatelets ≥ 80 x 109 /L, d)\tCalculated creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula), e)\tSerum bilirubin ≤ 1.5 x ULN (or ≤ 2.5 x ULN in the presence of documented Gilbert‘s Syndrome [unconjugated hyperbilirubinemia] or liver metastases), f)\tAST/ 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)\tInternational normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ ULN + 4 seconds.\n- 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.\n- Successful tumor tissue sampling by surgery, including presence of TILs in the tumor tissue in the pathological evaluation (refer to section 4.4.2).\n- Successful TIL expansion defined as obtaining the final CC-38 drug product of ...[redacted information].\n- Patient is 18 years or older at the time of signing the informed consent form.\n- 3.\tPatient weight above >50 kg."}

Exclusion criteria

• {"criterion_text":"- 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.\n- [redacted information]\n- Patient has received an organ and/or allogenic stem cell transplant.\n- Patient has known acute or chronic infection with hepatitis B or C virus.\n- Patient has known Human Immunodeficiency Virus HIV infection (seropositive for HIV antibody).\n- Patient has known infection with syphilis.\n- Patient has known bone-marrow aplasia.\n- Patient has known chronical urinary tract infection and/or acute urothelial toxicity from previous cytotoxic chemotherapy, radiation therapy, or urinary flow obstructions.\n- 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.\n- Patient is unable to comply with trial procedures, restrictions, or requirements.\n- 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.\n- Patient has any of the following pulmonary conditions: a)\tforced expiratory volume in 1 second (FEV1) < 60%, b)\tactive obstructive chronic pulmonary disease, c)\toxygen dependence as defined by a blood oxygen saturation that can only be maintained above 92% by oxygen inhalation (finger oxygen detection method), d)\tother pulmonary conditions that increase the anesthesiologic risk.\n- Patient received last palliative radiotherapy within less than 4 weeks prior enrollment – where RECIST 1.1 evaluable metastases are within the radiation area.\n- Patient received minor surgery within less than 3 weeks prior enrollment.\n- 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.\n- 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.\n- Patient has bone metastasis only.\n- Patient has known hypersensitivity to any component of the trial regimen.\n- For colorectal cancer: Patient has been diagnosed with histologically or cytologically proven BRAF-V600 positive CRC.\n- 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.\n- Patient has a current or history of central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression.\n- 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.\n- Patients who require therapeutic anticoagulant therapy or are otherwise at increased risk of bleeding events.\n- 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.\n- Patient has any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] or acquired immune deficiency syndrome [AIDS]).\n- 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.\n- 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."}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured as incidence of TEAEs and occurrence of severity grade ≥3 AEs according to NCI CTCAE v5.0; and proportion of patients receiving ≥2 TIL administrations without TEAEs preventing TIL administration."}

Secondary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Proportion of patients with CR or PR within first 6 months after start of CC-38 administration, assessed by Investigator per RECIST 1.1 and iRECIST."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Time from start of treatment to disease progression (per Investigator assessment using RECIST 1.1 and iRECIST) or death from any cause."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Time from start of treatment to disease progression as assessed by Investigator per RECIST 1.1 and iRECIST."}
• {"endpoint_text":"- Overall survival (OS), defined as time from start of treatment to time of death from any cause","definition_or_measurement_approach":"Time from start of treatment to death from any cause."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"PSA level changes from baseline until 6 months; PSMA PET-CT assessments at baseline and after third CC-38 administration."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Changes in specified biomarkers (e.g., CEA, CA-19-9) from baseline until 6 months after start of treatment."}

Germany

Earliest CTIS Part Ii Submission Date

07-07-2025

Latest Decision Or Authorization Date

12-03-2026

Processing Time Days

248

Number Of Sites

1

Number Of Participants

12

Primary sponsor

Full Name

CuraCell Holding AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Third parties

• {"country":"Germany","full_name":"Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH","duties_or_roles":"sponsorDuties codes: 1, 10, 11, 5, 6, 7, 8","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Zellwerk GmbH","duties_or_roles":"sponsorDuties codes: 14, 15 (\"IMP labeling and distribution\"), 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Krankenhaus Nordwest GmbH","duties_or_roles":"sponsorDuties codes: 14, 15 (\"IMP distribution, Pathological evaluation of tumor tissue\"), 4","organisation_type":"Hospital/Clinic/Other health care facility"}