MIDRIX-LUNG-002 for Metastatic non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Before patient screening, written informed consent must be given for the interventional study according to ICH/GCP and institutional practice.\n- Substudy I: non-squamous histology: Cohort 3: metastatic or locally advanced NSCLC progressive (including immune unconfirmed progressive disease) on anti-PD-1 monotherapy or in the maintenance phase of an anti-PD-1 therapy-containing regimen per SOC, and fulfilling the criteria of treatment beyond progression1. Patients must have had stable disease or a partial response as best response on prior anti-PD-1 therapy. Cohort 3B: progressing in the maintenance phase of an anti-PD-1 therapy-containing regimen, e.g. cisplatin/carboplatin-pemetrexed-pembrolizumab or cisplatin/carboplatin-pemetrexed-cemiplimab.\n- Substudy I: non-squamous histology: Cohort 4: metastatic or locally advanced NSCLC previously treated with an anti-PD-1 therapy-containing regimen that was discontinued after a maximum duration per SOC and eligible for anti-PD-1 therapy.\n- Substudy II: squamous histology: Cohort 1: metastatic NSCLC that will start on an anti-PD-1 therapy-containing regimen. Cohort 1A: pembrolizumab or cemiplimab monotherapy (PD-L1 TPS ≥ 50%).\n- Substudy II: squamous histology: Cohort 1: metastatic NSCLC that will start on an anti-PD-1 therapy-containing regimen. Cohort 1B: carboplatin-paclitaxel-pembrolizumab or carboplatin-paclitaxel-cemiplimab.\n- Substudy II: squamous histology: Cohort 2: metastatic NSCLC not progressive after completion of induction with carboplatin-paclitaxel-pembrolizumab or carboplatin-paclitaxel-cemiplimab.\n- Substudy II: squamous histology: Cohort 3: metastatic or locally advanced NSCLC progressive (including immune unconfirmed progressive disease) on anti-PD-1 monotherapy or in the maintenance phase of an anti-PD-1 therapy-containing regimen per SOC, and fulfilling the criteria of treatment beyond progression1. Patients must have had stable disease or a partial response as best response on prior anti-PD-1 therapy. Cohort 3A: progressing on anti-PD-1 monotherapy, e.g. pembrolizumab or cemiplimab (PD-L1 TPS ≥ 50%, no previous platinum-based chemotherapy).\n- Substudy II: squamous histology: Cohort 3: metastatic or locally advanced NSCLC progressive (including immune unconfirmed progressive disease) on anti-PD-1 monotherapy or in the maintenance phase of an anti-PD-1 therapy-containing regimen per SOC, and fulfilling the criteria of treatment beyond progression1. Patients must have had stable disease or a partial response as best response on prior anti-PD-1 therapy. Cohort 3B: progressing in the maintenance phase of an anti-PD-1 therapy-containing regimen, e.g. carboplatin-paclitaxel-pembrolizumab or carboplatin-paclitaxel-cemiplimab.\n- Substudy II: squamous histology: Cohort 4: metastatic NSCLC previously treated with an anti-PD-1 therapy-containing regimen that was discontinued after a maximum duration per SOC and eligible for anti-PD-1 therapy.\n- At least 1 measurable lesion per RECIST v1.1 at screening.\n- ECOG performance status 0 to 1.\n- Male or female participants age ≥ 18 years at screening.\n- Estimated life-expectancy > 12 weeks.\n- Documented brain metastasis must be either asymptomatic or stabilized after adequate radiotherapeutic treatment as per institutional practice.\n- Adequate organ function, including:1. Adequate bone marrow reserve: absolute neutrophil count > 1500/μL, platelet count > 100000/μL, and Hb > 9.0 g/dL. 2. For patients receiving chemotherapy, adequate renal function as defined by eGFR > 45 mL/min according to the Cockcroft-Gault formula. 3. Adequate hepatic function as defined by total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin within normal limits for participants with total bilirubin levels >1.5 x ULN; AST and ALT ≤ 3 x ULN or ≤ 5 x ULN if there is liver involvement by the tumor.\n- For Leukapheresis: Having passed all tests defined in the institutional Leukapheresis Donor Fitness Screening, including:1. Adequate peripheral vein access to perform leukapheresis. 2. Adequate coagulation function defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless the participant is receiving anticoagulant therapy. In this case, these criteria are not applicable or cannot be evaluated. 3. Negative test results for HBs-antigen, anti-HBc-serology, anti-HCV serology, anti-HIV1-2 serology, anti-CMV IgM, anti-Syphilis (Treponema pallidum) serology. 4.Negative test results for Epstein-Barr virus (IgM) and for Toxoplasmosis (IgM). 5. For female participants: a negative serum beta-HCG test result within 28 days before the day of leukapheresis.\n- For female participants with child-bearing potential, the willingness to follow contraceptive guidance and pregnancy testing during the projected duration of the trial (see Appendix B for Contraceptive Guidance and Pregnancy Testing). Female participants must have a negative serum pregnancy test at screening.\n- For male participants having a partner with child-bearing potential: agreement to use contraception during the projected duration of the trial, starting with the screening visit through 90 days after the last dose of trial treatment. Sperm donation must have been performed before anti-cancer treatment as per standard practice.\n- Histologically or cytologically proven diagnosis of NSCLC, newly diagnosed or recurrent stage IV, or stage IIIB-C not amenable to radical chemoradiotherapy (per AJCC 9th Edition).\n- Substudy I: non-squamous histology: Cohort 1: metastatic or locally advanced NSCLC that will start on an anti-PD-1 therapy-containing regimen. Cohort 1A: pembrolizumab or cemiplimab monotherapy (PD-L1 TPS ≥ 50%).\n- Substudy I: non-squamous histology: Cohort 1: metastatic or locally advanced NSCLC that will start on an anti-PD-1 therapy-containing regimen. Cohort 1B: cisplatin/carboplatin-pemetrexed-pembrolizumab or cisplatin/carboplatin-pemetrexed-cemiplimab.\n- Substudy I: non-squamous histology: Cohort 2: metastatic or locally advanced NSCLC not progressive after completion of induction with cisplatin/carboplatin-pemetrexed-pembrolizumab or cisplatin/carboplatin-pemetrexed-cemiplimab. Maintenance pemetrexed is allowed per investigator’s choice.\n- Substudy I: non-squamous histology: Cohort 3: metastatic or locally advanced NSCLC progressive (including immune unconfirmed progressive disease) on anti-PD-1 monotherapy or in the maintenance phase of an anti-PD-1 therapy-containing regimen per SOC, and fulfilling the criteria of treatment beyond progression1. Patients must have had stable disease or a partial response as best response on prior anti-PD-1 therapy. Cohort 3A: progressing on anti-PD-1 monotherapy, e.g. pembrolizumab or cemiplimab (PD-L1 TPS ≥ 50%, no previous platinum-based chemotherapy)."}

Exclusion criteria

• {"criterion_text":"- Presence of oncogenic driver genomic alterations (EGFR, ALK, ROS1, RET, BRAF V600, NTRK, MET, HER2), as determined by existing local test results, for which a targeted therapy is available. Patients with KRAS mutations, including KRAS G12C mutations, are eligible if no targeted therapy is available at the time of screening.\n- Autoimmune disease requiring treatment with immunosuppressive medication at the time of the study. 1.Patients with a history of auto-immune hypothyroidism on a stable dose of thyroid hormone replacement may be eligible. 2. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible. 3. Patients with eczema, psoriasis, lichen simplex, or vitiligo with dermatologic manifestations only may be eligible provided the disease is well controlled at screening and only requires low potency topical steroids.\n- Any chronic or active concomitant infection (bacterial, viral, fungal) that is uncontrolled or requires systemic therapy.\n- Known infection with hepatitis B (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection.\n- Active tuberculosis.\n- Prior allogeneic stem cell or solid organ transplantation.\n- Interstitial lung disease.\n- Known hypersensitivity or allergy to one of the vaccine substances.\n- Chronic comorbidity (such as asthma, COPD, heart failure, renal failure, arterial hypertension or diabetes mellitus) that is uncontrolled or not stabilized under medication at the time of study enrolment, or stable yet severe enough to constitute an unwarranted high risk for the investigational cellular therapy.\n- For female participants: pregnancy or lactation or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 90 days after the last dose of trial treatment.\n- Any organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent and preclude participation in the full protocol and follow-up.\n- For cohort 3: progressive disease as best response to anti-PD-1 therapy (primary resistance) or clinical or radiographic signs of hyperprogressive disease.\n- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before enrolment in the trial.\n- Prior treatment with autologous or allogeneic dendritic cell-based vaccines.\n- Prior treatment with anti-CTLA-4 therapy or anti-PD-L1 therapy for metastatic NSCLC.\n- Receipt of a live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: participants, if enrolled, should not receive a live attenuated vaccine while receiving study intervention and up to 30 days after the last dose of study intervention.\n- Participants who have received more than one line of prior anti-PD-(L)1 therapy, either alone or in any combination, are excluded except with the following exception: Patients who completed treatment with an anti-PD-(L)1 therapy for locally advanced NSCLC after chemoradiotherapy or as a (neo-)adjuvant therapy for resectable NSCLC, and are subsequently treated with an anti-PD-1 therapy for metastatic disease, may be included.\n- Concomitant participation in another clinical interventional trial. Subjects who are participating in another interventional trial and have completed the progression-free survival follow-up are eligible.\n- NSCLC with large-cell neuro-endocrine or sarcomatoid histology.\n- Prior malignancy, except for adequately treated non-melanoma skin carcinoma, in situ cancer of the bladder or the cervix, localized prostate cancer, ductal breast carcinoma in situ, or any other cancer for which the patient has been disease-free for at least two years.\n- Untreated brain metastases with neurological symptoms or brain metastasis requiring a daily intake of steroids of > 10 mg oral prednisolone or equivalent.\n- Leptomeningeal disease.\n- Persistent toxicities > CTCAE grade 2, including immune related adverse events (irAE), caused by a previous anticancer therapy.\n- Disease requiring chronic treatment with systemic glucocorticosteroids with a daily dose > 10 mg oral prednisolone or equivalent. Inhaled corticosteroids and topical corticosteroids on skin sites are allowed."}

Primary endpoints

• {"endpoint_text":"- Toxicity as defined by the Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v.5.0). Toxicity will be assessed during the interventional treatment phase of the trial from leukapheresis until three months after the last vaccine dose.","definition_or_measurement_approach":"Toxicity measured and graded using CTCAE v5.0; assessment period from leukapheresis until three months after the last vaccine dose (during the interventional treatment phase)."}

Secondary endpoints

• {"endpoint_text":"- Overall response rate (ORR%) based on investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; duration of response; median progression-free survival (mPFS, months); 1-year PFS (%) based on investigator assessment per RECIST 1.1; median overall survival (mOS, months); 1-year OS (%).","definition_or_measurement_approach":"Tumor response assessed by investigator per RECIST v1.1; ORR, duration of response, PFS and OS measured in months and percentages at specified timepoints."}
• {"endpoint_text":"- Vaccine-induced immune responses as measured by in vitro immunomonitoring tests (antigen-specific T-cell reactivity). Immune responses will be measured after each DC vaccination and at prespecified timepoints during the follow-up period.","definition_or_measurement_approach":"Immune response assessment via in vitro immunomonitoring tests measuring antigen-specific T-cell reactivity at specified timepoints after each DC vaccination and during follow-up."}
• {"endpoint_text":"- Success rate (%) of manufacturing sufficient DCs for vaccination, which is defined as the production of DC aliquots for ≥ 3 vaccination rounds.","definition_or_measurement_approach":"Manufacturing success defined as production of DC aliquots sufficient for ≥3 vaccination rounds; reported as percentage success rate."}
• {"endpoint_text":"- Health-related quality of life by means of the EORTC QLQ-C30 and EORTC QLQ-LC29 questionnaires, measured before and during the interventional treatment phase of the trial.","definition_or_measurement_approach":"HRQoL measured using EORTC QLQ-C30 and QLQ-LC29 questionnaires at baseline and during the interventional treatment phase."}

Belgium

Earliest CTIS Part Ii Submission Date

11-08-2025

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

31

Number Of Sites

1

Number Of Participants

64

Primary sponsor

Full Name

Universitair Ziekenhuis Gent

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium

Third parties

• {"country":"","full_name":"FICO","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Kom Op Tegen Kanker","duties_or_roles":"Monetary support","organisation_type":""}