OMTX705 for Non-small cell lung cancer (non-squamous), advanced/metastatic

Inclusion criteria

• {"criterion_text":"- Capable of giving a signed informed consent form (ICF) as described in Section 12.2 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. A signed ICF must be obtained prior to conducting any study specific procedures.\n- Women of childbearing potential (WOCBP) and men with sexual partners who are WOCBP must be willing to adhere to contraceptive requirements.\n- Suitable venous access for safe drug administration and the study-required drug concentration and pharmacodynamics sampling.\n- Have provided tumor tissue from locations not radiated prior to biopsy; formalin-fixed specimens after the patient has been diagnosed with metastatic disease will be preferred for determination of PD-L1 status prior to randomization (not required for Part 1). Biopsies obtained prior to receipt of adjuvant/neoadjuvant chemotherapy will be permitted if recent biopsy is not feasible.\n- Male and female patients aged 18 years and older.\n- Have a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b subcategory, based on the seventh edition of the American Joint Committee on Cancer Staging Manual) non-squamous NSCLC or stage III that has exhausted available locoregional therapies, or if they are contraindicated or locally unavailable\n- PD-L1 TPS, ranging from 0 to 100%, in a tumor biopsy measured locally with an approved test. NOTE: In Part 2, the PD-L1 TPS result should be available for randomization\n- Have confirmation that any targeted therapy (EGFR-, ALK-directed, or any other targeted therapy) is not indicated. Documentation of absence of tumor-activating EGFR mutations AND absence of ALK gene rearrangements OR presence of Rat sarcoma (RAS) mutations is required\n- Measurable disease by RECIST 1.1 on computed tomography (CT) scan, PET/CT or magnetic resonance imaging (MRI) scan. Image tests outside the screening period are valid if performed no more than 3 weeks before consent signature and otherwise fulfil protocol criteria\n- Have not received prior systemic treatment for their advanced/metastatic NSCLC. Patients who received adjuvant or neoadjuvant therapy for initial stages I to III are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease.\n- Eastern Cooperative Oncology Group Performance (ECOG) performance status 0-1.\n- Adequate bone marrow, hepatic and renal function: •\tTotal bilirubin ≤1.5 times the upper limit of normal (ULN) or total bilirubin <3.0×ULN with direct bilirubin within normal range in patients with documented Gilbert’s syndrome. •\tAST and ALT ≤3×ULN (if liver metastases are present, then ≤5×ULN is allowed). •\tCalculated creatinine clearance (CrCL) of ≥45 mL/minute using the Cockcroft Gault formula. •\tHemoglobin ≥9.0 g/dL (whole or partial blood transfusions not allowed in the 2 previous weeks). •\tAbsolute neutrophil count (ANC) ≥1.5×109/L (growth factors like granulocyte-colony stimulating factor [G-CSF] are not allowed in the 2 previous weeks). •\tPlatelet count ≥100×109/L (platelet transfusions in the 2 previous weeks are not allowed)."}

Exclusion criteria

• {"criterion_text":"- Has predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the patient is ineligible.\n- Has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thoracentesis, paracentesis, or pleurodesis) is eligible.\n- Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or compromised ability to provide written informed consent.\n- Previous or concurrent cancer that is distinct in primary site or histology from NSCLC within 3 years prior to randomization, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]).\n- Uncontrolled or significant cardiovascular disease defined by the New York Hearth Association (NYHA) classification III or IV.\n- History of cerebrovascular stroke or myocardial infarction within the previous 3 months.\n- Grade ≥2 peripheral neuropathy.\n- The patient is under chronic systemic steroids. Patients with asthma requiring intermittent use of bronchodilators or inhaled steroids are eligible for the study.\n- Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long acting agents, such as piroxicam).\n- Is unable or unwilling to take folic acid or vitamin B12 supplementation.\n- History of autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses >10 mg/day).\n- Treatment with systemic anticancer treatments, investigational products, or major surgery within 4 weeks before the first dose of study drug or 5 half-lives elimination period for drug therapies, whichever is shorter. Patients treated with systemic anticancer therapies/investigational drugs should have recovered from previous treatment toxicity to Grade 1, baseline (except alopecia). Patients with endocrinopathies should have the replacement treatment in a stable dosing regimen.\n- Patients who discontinued prior treatment with any immune checkpoint due to irAEs, irrespective of grade, recovery, or need for continued steroid therapy. Also, patients without formal contraindication due to previous irAE are not eligible if the AE has not resolved to Grade 1 or better and/or still requires steroids (>10 mg of prednisone equivalent per day) for ongoing management.\n- Patients with interstitial lung disease or a history of pneumonitis requiring oral or IV glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary.\n- History of myocarditis.\n- Patients who received live vaccines within 30 days of enrollment.\n- Known hepatitis B virus surface antigen seropositive or detectable hepatitis C infection viral load. NOTE: Patients who have positive hepatitis B surface antigen antibody can be included but must have an undetectable hepatitis B viral load. Patients receiving antiviral therapy for hepatitis B for any reason are excluded.\n- Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must meet the following criteria: •\thave CD4+ T-cell (CD4+) counts ≥350 cells/µL. •\thave not had an opportunistic infection within the past 12 months. Patients on prophylactic antimicrobials can be included in the trial. •\tshould be on established antiretroviral therapy for at least 4 weeks. •\thave an HIV viral load of less than 400 copies/mL prior to enrollment. •\tknown history of any other relevant congenital or acquired immunodeficiency other than HIV infection.\n- Known or suspected allergy to study treatment or related products, and specifically patients with a prior history of life-threatening reaction to polysorbate 20.\n- Women who are pregnant, breastfeeding, or trying to become pregnant.\n- Male patients wishing to father children, planning for future sperm banking, or expressing concerns about sterility.\n- Before the first dose of trial treatment: •\tHas received prior systemic cytotoxic chemotherapy or immunotherapy for metastatic disease •\tHas received antineoplastic biological therapy (e.g., erlotinib, osimertinib, crizotinib, cetuximab) NOTE: Patients with initial locoregional disease are eligible after progression to chemoradiation/surgery ± immune checkpoint therapies.\n- Received radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study treatment.\n- Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate, provided they are clinically stable for at least 2 weeks and have no evidence of new or enlarging brain metastases and are off steroids 3 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Patients with asymptomatic brain metastases (i.e., no neurological symptoms, no requirement for corticosteroids, and no lesion >1.5 cm) may participate but will require regular imaging of the brain as a site of disease. Patients without CNS symptoms are not required to have brain images to participate.\n- Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to randomization.\n- Cardiac arrhythmias requiring anti-arrhythmic therapy. NOTE: Pacemakers, beta blockers, or digoxin are permitted.\n- Active infection requiring parenteral or oral antibiotics. Antibiotics given for prophylaxis are allowed. They are also allowed for minor localized infections like cystitis, tonsillitis, or localized skin infections.\n- Evidence of a serious uncontrolled medical disorder that, in the opinion of the Investigator or Medical Monitor, makes it unwise for the patient to participate in the study or that might jeopardize compliance with the protocol."}

Primary endpoints

• {"endpoint_text":"- Part 1: The safety and tolerability of OMTX705 in combination with tislelizumab, carboplatin and pemetrexed will be assessed by: •\tThe nature and frequency of DLTs. •\tFrequency, duration, and severity of treatment emerging adverse events (TEAEs) per Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).","definition_or_measurement_approach":"Assessment of DLTs (nature and frequency); TEAEs assessed by frequency, duration, and severity per CTCAE v5.0."}
• {"endpoint_text":"- •\tChanges in vital signs, serum chemistry and hematology. •\tTreatment modifications condensed as percentage of relative dose intensity and other dose endpoints. •\tThe MTD dose or recommended Part 2 dose.","definition_or_measurement_approach":"Monitoring of vital signs, laboratory chemistry and hematology; calculation of treatment modifications as percentage relative dose intensity; determination of MTD or recommended Part 2 dose based on DLTs."}
• {"endpoint_text":"- Part 2: Objective response rate (ORR), as determined by the Investigator, according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).","definition_or_measurement_approach":"ORR measured by Investigator assessment per RECIST 1.1."}

Secondary endpoints

• {"endpoint_text":"- Part 1 and 2: Additional efficacy endpoints will be evaluated by using RECIST 1.1: •\tResponse-associated endpoints: disease control rate (DCR)=complete response (CR) + partial response (PR) + stable disease (SD) ≥ 1st, 2nd and 3rd postbaseline computed tomography scan evaluation, duration of response (DoR), and time to response.","definition_or_measurement_approach":"Response-associated endpoints assessed by RECIST 1.1 including DCR (CR+PR+SD at specified postbaseline scans), DoR, and time to response."}
• {"endpoint_text":"- •\tTime-to-event efficacy endpoints: progression-free survival (PFS), proportion of participants without progression/death at 3, 6, and 12 months and every 3 months thereafter. Overall survival (OS) and proportion of participants alive at 3, 6, 12, 18 and 24 months.","definition_or_measurement_approach":"Time-to-event endpoints including PFS and OS assessed with standard survival analyses; proportions alive/progression-free at specified timepoints."}
• {"endpoint_text":"- Additional safety data will be evaluated by assessing: •\tFrequency, duration, seriousness, relatedness, and severity of TEAEs, per CTCAE v5.0 •\tChanges in vital signs, serum chemistry and hematology. •\tTreatment modifications condensed as percentage of relative dose intensity and other dose endpoints.","definition_or_measurement_approach":"Safety assessments per CTCAE v5.0 for TEAEs plus laboratory and vital sign monitoring and dose intensity calculations."}
• {"endpoint_text":"- Part 1 and Part 2 immunogenicity of OMTX705 will be assessed by: •\tQuantification (titer) of anti-drug antibodies (ADAs) against OMTX705 and percentage of ADA positive participants.","definition_or_measurement_approach":"Immunogenicity measured by ADA titers and percentage ADA-positive participants."}
• {"endpoint_text":"- Part 1 and Part 2 pharmacokinetics profile of OMTX705 with pemetrexed/carboplatin /tislelizumab: •\tBlood concentrations of conjugated antibody and unconjugated payload (TAM470) listed and summarized using descriptive statistics.","definition_or_measurement_approach":"PK measured by blood concentrations of conjugated antibody and unconjugated payload (TAM470), summarized using descriptive statistics."}

Spain

Earliest CTIS Part Ii Submission Date

24-11-2025

Latest Decision Or Authorization Date

12-12-2025

Processing Time Days

18

Number Of Sites

11

Number Of Participants

88

Primary sponsor

Full Name

Oncomatryx Biopharma S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Optimapharm d.o.o.

Third parties

• {"country":"Spain","full_name":"CTI Laboratory Services Spain S.L.","duties_or_roles":"OMTX705 pharmacokinetic bioanalysis","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"OMTX705 import, IMPs labelling, packaging, IMPs supply/re-supply to the sites, IMPs storage, IMPs destruction; IMPs release","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"tislelizumab importer and QP release in Europe","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"World Courier","duties_or_roles":"OMTX705 logistics","organisation_type":"Industry"}
• {"country":"France","full_name":"CERTARA","duties_or_roles":"OMTX705 pharmacokinetic non-compartimental analysis","organisation_type":"Health care"}
• {"country":"Spain","full_name":"Centro de Investigación del Cáncer-Universidad de Salamanca","duties_or_roles":"biomarkers detection (OMTX705 pharmacodynamics profiling)","organisation_type":"Industry"}
• {"country":"Taiwan","full_name":"Eirgenix Inc.","duties_or_roles":"Drug substance (OMTX705) manufacturer","organisation_type":"Pharmaceutical company"}
• {"country":"Taiwan","full_name":"Formosa Laboratories Inc.","duties_or_roles":"Drug product (OMTX705) manufacturer","organisation_type":"Pharmaceutical company"}
• {"country":"Croatia","full_name":"Optimapharm d.o.o.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Polar Expres","duties_or_roles":"biological sample logistics, laboratory material provider, lab kits building and supply to the sites","organisation_type":"Industry"}
• {"country":"France","full_name":"Cerba","duties_or_roles":"biomarkers detection (OMTX705 pharmacodynamics profiling)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"China","full_name":"Beigene (Beijing) Biotechnology Co. Ltd.","duties_or_roles":"tislelizumab supplier","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Anapharm Europe S.L.","duties_or_roles":"immunogenicity analysis (antibody anti-drug or ADA detection)","organisation_type":"Pharmaceutical company"}