IOMX-0675 for Advanced/metastatic solid tumors | Non-small cell lung cancer | Gastric cancer | Gastro-esophageal junction cancer | Mesothelioma | Renal cell carcinoma | Colorectal cancer (MSS/pMMR)

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years (or legal age of consent in the country) at the time of signing the informed consent form\n- For monotherapy backfill cohorts: histologically confirmed: a) non-small cell lung cancer (NSCLC) treated with a cytotoxic systemic regimen, immune checkpoint inhibitor and/or targeted therapy, or b) gastric or gastro-esophageal junction cancer treated with a fluoropyrimidine containing systemic regimen, or c) mesothelioma treated with a cytotoxic systemic regimen and/or immune checkpoint inhibitor, or d) kidney cancer (RCC) treated with a targeted (anti-angiogenic) and/or immune checkpoint inhibitor therapy.\n- For combination cohorts: histologically and molecularly confirmed advanced or metastatic MSS or pMMR colorectal cancer having received one prior line of therapy containing a fluoropyrimidine-containing regimen AND anti-angiogenetic and/or anti-EGFR therapy.\n- Cytologically or pathologically confirmed locally advanced, inoperable, and/or metastatic cancer\n- All subjects must have received at least one previous line of systemic therapy for the tumor type under investigation\n- ECOG Performance Status of 0 or 1\n- For male subjects with female partners of childbearing potential and female subjects of childbearing potential: agreement to use contraception during treatment and for ≥ 3 months after the last dose of IOMX-0675\n- Recovery from all toxicities of previous anti-cancer therapy (including radiotherapy) to Grade ≤ 1 or stable Grade 2 (NCI CTCAE v5), except for alopecia, asymptomatic endocrinopathies, or toxicities managed with stable replacement therapy (e.g., hypothyroidism, adrenal insufficiency)\n- Adequate organ function within 7 days prior to the first IMP administration, as assessed by: a) ANC ≥ 1200/µL b) Platelets ≥ 75,000/µL c) Hemoglobin ≥ 9 g/dL d) Total bilirubin ≤ 1.5×ULN (or ≤ 3.0×ULN for Gilbert's disease) e) AST and ALT ≤ 3.0×ULN (≤ 5.0×ULN with hepatic metastases) f) Albumin WNL g) eGFR ≥ 50 mL/min (CKD-EPI formula) h) No transfusions, substitutions, or stimulating factors within 2 weeks prior to blood testing\n- At least one evaluable lesion by iRECIST criteria (backfill cohorts of monotherapy and all combination cohort)\n- Willingness and ability to undergo serial tumor biopsies (baseline and post-baseline) (backfill cohorts of monotherapy and all combination cohort)"}

Exclusion criteria

• {"criterion_text":"- Significant uncontrolled cardiovascular disease or NYHA class III or IV cardiac insufficiency\n- History of Grade > 3 immune-related adverse events (irAEs) with prior immunotherapy\n- Unresolved toxicity > Grade 1 from prior therapies (except alopecia and toxicities managed with stable substitution therapy)\n- Clinically relevant findings on screening 12-lead ECG, per investigator judgment\n- Psychological conditions potentially compromising trial compliance, per investigator judgment\n- History of pneumonitis or interstitial lung disease (combination cohorts only)\n- More than four prior lines of systemic therapy (for backfill monotherapy and combination cohorts only)\n- Pregnancy or breastfeeding\n- Known symptomatic CNS metastases and/or carcinomatous meningitis a) Exception: stable, previously treated brain metastases (no progression on MRI for ≥ 4 weeks, no neurologic symptoms at baseline, no steroids for ≥ 7 days prior to study medication) b) Patients eligible for complete surgical resection of brain metastases are excluded\n- History of significant cerebrovascular disease (e.g., stroke) within 6 months or Grade ≥ 3 sensory/motor neuropathy\n- Treatment with anti-cancer or investigational drugs within 5 half-lives or 30 days prior to first drug administration (whichever is shorter)\n- Pregnancy or breastfeeding\n- Known symptomatic CNS metastases and/or carcinomatous meningitis a) Exception: stable, previously treated brain metastases (no progression on MRI for ≥ 4 weeks, no neurologic symptoms at baseline, no steroids for ≥ 7 days prior to study medication) b) Patients eligible for complete surgical resection of brain metastases are excluded\n- Active autoimmune disease or syndrome requiring systemic steroids or immunosuppressants, except for: a) Inhaled corticosteroids b) History of autoimmune disease not requiring systemic treatment for ≥ 2 years (except autoimmune-induced thyroid dysfunction) c) Vitiligo or resolved childhood asthma/atopy d) Local steroid injections e) Hypothyroidism stable on hormone replacement\n- Known or suspected hypersensitivity to IOMX-0675 or its excipients (L-histidine, L-arginine polysorbate 80)"}

Primary endpoints

• {"endpoint_text":"- Identification of a RP2D and combination dose of IOMX-0675 based on the comparative integration of this information across dose levels:","definition_or_measurement_approach":""}
• {"endpoint_text":"- •\tIncidence of DLTs attributable to IOMX-0675 and pembrolizumab, where applicable, at each dose level and identification of a maximum tolerated dose (MTD).","definition_or_measurement_approach":"Incidence of dose-limiting toxicities (DLTs) attributable to IOMX-0675 and pembrolizumab at each dose level; used to identify MTD."}
• {"endpoint_text":"- •\tType, incidence, and severity of treatment related AEs according to the NCI CTCAE version 5.0 at each dose level.","definition_or_measurement_approach":"Assessment of adverse events by type, incidence and severity graded per NCI CTCAE v5.0 at each dose level."}
• {"endpoint_text":"- •\tCalculation of at least the following parameters: Cmax, tmax, AUClast, t½ from concentration time information.","definition_or_measurement_approach":"Pharmacokinetic parameters (Cmax, tmax, AUClast, t½) calculated from concentration–time data."}
• {"endpoint_text":"- •\tMaximum receptor occupancy","definition_or_measurement_approach":"Measurement of receptor occupancy (maximum) as a pharmacodynamic biomarker."}
• {"endpoint_text":"- Dose selection will be further supported by:","definition_or_measurement_approach":""}
• {"endpoint_text":"- •\tObserved clinical activity (see secondary endpoints)","definition_or_measurement_approach":"Clinical activity assessed via secondary endpoints (e.g., ORR, DoR, PFS)."}
• {"endpoint_text":"- •\tBiomarker activity","definition_or_measurement_approach":"Assessment of biomarker activity to support dose selection."}

Secondary endpoints

• {"endpoint_text":"- Overall response rate (ORR)","definition_or_measurement_approach":"Overall response rate assessed per standard response criteria (e.g., iRECIST referenced elsewhere)."}
• {"endpoint_text":"- Duration of Response (DoR)","definition_or_measurement_approach":"Time from first documented response to progression or death."}
• {"endpoint_text":"- Progression free survival (PFS)","definition_or_measurement_approach":"Time from treatment start to documented disease progression or death."}

Spain

Earliest CTIS Part Ii Submission Date

28-03-2025

Latest Decision Or Authorization Date

03-04-2025

Processing Time Days

6

Number Of Sites

5

Number Of Participants

110

Primary sponsor

Full Name

iOmx Therapeutics AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Granzer Pharmaceutical Services GmbH","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Patheon Italia S.p.A.","duties_or_roles":"code 15; Drug Product Manufacturing","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"SGS Analytics Germany GmbH","duties_or_roles":"code 15; Laboratory logistics","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Alira Health","duties_or_roles":"codes 1,10,11,5,6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Discovery Life Sciences LLC","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Patheon Biologics B.V.","duties_or_roles":"code 15; Drug Substance Manufacturing","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Aptuit (Verona) S.r.l.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"TFS Trial Form Support AB","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Nuvisan GmbH","duties_or_roles":"code 15; Packing and Labeling","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"SGS Analytics Germany GmbH (Berlin address)","duties_or_roles":"codes 4,5","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}