TUB-030 for Advanced solid tumors | Head and neck squamous cell carcinoma | Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Male or non-pregnant, non-breastfeeding female aged 18 years or older at the date of consent.\n- Eastern Cooperative Oncology Group (ECOG) 0-1;\n- Have a life expectancy of >12 weeks for disease-related mortality, as evaluated by the INV\n- In the opinion of the INV, the patient must be able and willing to understand and give signed informed consent, and to comply with the requirements and restrictions listed in the ICF and this protocol\n- Patients must have adequate archival tissue available: either a formalin-fixed and paraffin-embedded [FFPE] block or a minimum of 6 (20 is preferred) unstained freshly cut sections should be submitted. If multiple specimens are available, the most recent sample with adequate tumor tissue should be selected. If archival tissue is unavailable, then unstained sections from a fresh tumor biopsy may be submitted. If a fresh tumor biopsy is performed, the criteria in Section 6.6.1 must be satisfied. Patients must sign an archival tissue release form for research purposes and determination of biomarker ([...]) expression. A requirement for a fresh biopsy may be waived at the Sponsor’s discretion at dose levels < X.Xmg/kg.\n- Women of childbearing potential (WOCBP) who are sexually active with a non-sterilized partner must use at least 1 highly effective method of contraception (with a failure rate of 1% per year) from the time of screening and must agree to continue using such precautions until the end of exposure, plus 5 half-lives and 6 months add-on in the case of patients of childbearing potential. Abstinence is acceptable only when this is in line with the preferred and usual lifestyle of the patient for the duration of the study treatment and the above-referred period after the end of the exposure. Periodic abstinence (e.g. calendar ovulation, symptom-thermal, post-ovulation methods), the rhythm method, and the withdrawal method are not acceptable methods of contraception\n- Males must use an effective barrier method of contraception without interruption if the patient is sexually active with an WOCBP until the end of exposure, 5 half-lives plus 6 months add-on after the end of treatment. In addition, their female partners who are WOCBP should agree to use 1 highly effective barrier method of contraception at the same time. Male patients should refrain from donating sperm during study participation and for 6 months after the last dose of the study drug.\n- Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B (HBV) anti-viral therapy for at least 4 weeks and have undetectable HBV viral load\n- Patients with history of hepatitis C viral (HCV) infection are eligible if HCV viral load is undetectable at screening\n- Human immunodeficiency virus (HIV)-infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as: A. Patients on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening. B. Patients on ART must have achieved and maintained virologic suppression, defined as confirmed HIV ribonucleic acid (RNA) level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening. C. Patients on ART must have been on stable regimen, without changes in drugs or dose modification, for at least 4 weeks before C1D1\n- (For Patients in Phase I Dose Escalation) Patients with locally advanced or metastatic disease that are intolerant or refractory to standard therapy or for which no standard therapy is judged appropriate by the INV.\n- Adequate hematologic function as indicated by: - Platelet count ≥100,000/mm3 (no transfusion or growth factors e.g. eltrombopag, romiplostim, or IL-11 within 2 weeks before first dose) - Hemoglobin ≥8.0 g/dL (no transfusion or growth factors e.g. erythropoietin [EPO], darbepoetin within 2 weeks before first dose) - Absolute neutrophil count (ANC) ≥1500/μL (no growth factors e.g. granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage-colony stimulating factor [GM-CSF] within 2 weeks before first dose) - International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN) in the absence of anticoagulation therapy. If patients are on anticoagulation therapy with a specific INR goal, INR should be within the therapeutic range for the medical indication.\n- (For Patients in Phase I Dose Escalation) Histologically confirmed diagnosis of tumors likely to express [...] including: HNSCC, NSCLC\n- (Phase I Backfill Cohorts and Phase 2a Dose Optimization, HNSCC) Unresectable or locally recurrent or metastatic HNSCC with primary tumor site arising from [...] independent of HPV status (high-risk HPV-specific testing or by p16 IHC) and XX-XX status (both HPV and XX-XX status must be known and documented)\n- (Phase I Backfill Cohorts and Phase 2a Dose Optimization, HNSCC) Must have progressed on or be refractory or intolerant to at least 1 prior line of therapy with SoC e.g. [...]-based therapy and either [...] agent or [...], if indicated, and no standard therapy is judged appropriate by the INV\n- (Phase I Backfill Cohorts and Phase 2a Dose Optimization, HNSCC) Patient was previously treated with a maximum of [X] prior lines of therapy in the advanced/metastatic setting.\n- (NSCLC) Histologically-confirmed NSCLC of (i) […] or, (ii) […] of the lung, or iii) […], iv) NSCLC not otherwise specified or poorly differentiated\n- (NSCLC) Patients without actionable gene alterations (AGAs; genes with approved targeted therapies) must have progressed on or be refractory to or intolerant of at least 1 line of [X]-based therapy, and [...] therapy (in absence of contraindications) in the recurrent/metastatic setting. Patients without AGAs must have received no more than [X] prior lines of therapy in the recurrent/metastatic setting.\n- (NSCLC) Patients with AGAs must have progressed on or be refractory or intolerant to at least [X] line of targeted therapy and at least [X] line of [X]-based therapy in the recurrent/metastatic setting. Patients with AGAs must have received no more than [X] prior lines of therapy in the recurrent/metastatic setting.\n- (NSCLC) Patients who have relapsed after curative [...]-based therapy and are not good candidates for repeated [X] -based therapy in the recurrent/metastatic setting as determined by the INV are allowed\n- (TNBC) Histologically or cytologically documented, locally recurrent, inoperable TNBC, or metastatic TNBC, for definition criteria, please refer to protocol incl crit #28\n- (TNBC) Must have progressed on or be refractory or intolerant to at least [X] prior lines of therapy with SoC for advanced/unresectable or metastatic breast cancer, e.g., [...] -compounds and if [...], patients must have received a combination of [...] and/or [...] if indicated ( [...] or [...] ), and no standard therapy is judged appropriate by the INV, for further details, please refer to protocol incl. crit # 29\n- Adequate hepatic function defined by: a total bilirubin level ≤1.5 × ULN, an aspartate aminotransferase (AST) level ≤2.5 × ULN, and an alanine aminotransferase (ALT) level ≤2.5 × ULN, ULN: For documented Gilbert's Syndrome, a total bilirubin <3 × ULN is accepted For patients with liver metastases, AST and ALT <5 × ULN is accepted\n- (TNBC) Patient was previously treated with a maximum of [X] prior lines of therapy in the advanced/metastatic setting\n- (TNBC) Breast cancer patients with skin-only disease may be eligible if the skin lesion(s) are measurable and after discussion with the Sponsor\n- (CRC) Unresectable, recurrent or metastatic colorectal adenocarcinoma\n- (CRC) Must have progressed on or be intolerant to at least [X] prior line of standard therapy in the recurrent/metastatic setting, which includes: a. At least one [...] combination with [...] and [...] b. [...] agent and/or [...] agent, if indicated c. [...] therapy for[...] tumors d.\t[...] if indicated e. [...] inhibitors if indicated f. Progression on prior immune checkpoint inhibitor therapy in microsatellite instability-high (MSI-H) / mismatch repair-deficient (dMMR) tumors \"\n- (CRC) Patient was previously treated with a maximum of [X] prior lines of therapy in the advanced/metastatic setting, and no standard therapy is judged appropriate by the INV\n- Adequate renal function defined by glomerular filtration rate ≥60 mL/min (according to the Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI, formula)\n- Patients who received anti-cancer treatment including [...], or other oral or investigational drugs must have had their last dose at least 4 weeks (6 weeks for [...]) or 5 half-lives, whichever is shorter, before C1D1 treatment with TUB-030\n- AEs related to prior therapy, radiotherapy or surgical procedures must resolve to ≤grade 1, exceptions to this include hyperpigmentation, discoloration (including vitiligo) of the skin and nails, stable immune-related toxicity such as hypothyroidism on hormone replacement, stable immune-related toxicities requiring up to 10 mg daily prednisone (or equivalent), or chronic peripheral sensory neuropathy grade ≤ 2.\n- For patients with known brain metastases evidence of clinically stable disease post radiation therapy is required prior to enrollment. The final dose of stereotactic radiation must have been administered ≥ 7 days, or the final dose of whole brain radiation must have been administered ≥ 14 days prior to C1D1\n- For patients who underwent radiotherapy (≥ 30% of the bone marrow or wide field) to sites outside the brain, the final dose of radiation must have been administered ≥ 28 days prior to C1D1. For patients who underwent palliative radiotherapy (≤ 30% of the bone marrow or wide field) the final dose of radiation must have been administered ≥14 days prior to C1D1\n- Radiologically measurable disease by RECIST v1.1 confirmed < 4 weeks before C1D1. A lesion in an irradiated field that shows progression according to RECIST v1.1 after irradiation is allowed;"}

Exclusion criteria

• {"criterion_text":"- Patient is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.\n- Surgery within 21 days before signing the ICF, unless the INV judges the patient is recovered at that time.\n- History of non-infectious ILD/pneumonitis/radiation pneumonitis that required steroid therapy or is suspected of having active ILD/pneumonitis based on imaging and symptoms\n- Diagnosis of grade ≥2 fever within 1 week before first dose of study drug. Patients with grade 1 fever may be eligible if in the judgement of the INV the fever is likely due to tumor and not infection\n- Active clinically significant corneal disease, or history of clinically significant corneal disease within 12 months prior to first dose of study drug\n- Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary, cardiovascular, respiratory, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the INV, would predispose the patient to the development of complications from the investigational agent\n- History of another malignancy with ongoing treatment or not yet free from disease for 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome\n- Documented other concurrent non-malignant comorbidities such as unstable or uncontrolled pectoral angina, myocardial infarction during the last 6 months, valvular heart disease that requires treatment, acute myocarditis, or congestive heart failure (CHF) (New York Heart Association III or IV). Coronary revascularization procedure within 180 days of study entry. Calculated QTc average (using the Fridericia correction calculation) of >470 msec\n- Any concurrent anti-cancer chemotherapy, radiotherapy (except for local radiation therapy of lesions that may cause imminent complications), hormonal therapy (except hormonal therapies acting on the hypothalamic-pituitary-gonadal axis i.e. luteinizing hormone-releasing hormone agonist/and agonists or hormone therapy for benign prostate neoplasm/hypertropia)\n- Live attenuated vaccines within 30 days prior to first dose of study drug\n- Patients with an active and symptomatic fungal, bacterial, or viral infection (including COVID-19).\n- History of hypersensitivity to exatecan or excipients of the TUB-030 formulation\n- Tumor with a histological diagnosis of liposarcoma or angiosarcoma\n- Patients currently receiving (or unable to stop prior to receiving the study intervention TUB-030) prohibited medication, e.g., strong CYP3A4, CYP1A2 inhibitors and strong CYP3A4 inducers\n- HNSCC only: HNSCC arising from paranasal sinus, salivary gland cancer, nasopharyngeal carcinoma\n- NSCLC only: History of a prior pneumonectomy\n- Disease that progressed on treatment with an ADC that is formulated with payloads that are either Dxd, exatecan, or SN38; treatment with an ADC with other payloads are allowed\n- Prior treatment with any drug or investigational agent targeting 5T4\n- Participation in interventional clinical studies either concurrently or within the previous 28 days or within 5 half-lives (whichever is shorter) of any investigational pharmacologic agents.\n- Patients with untreated spinal cord compression or cerebrovascular accident/stroke within <6 months of first dose of study drug\n- History of progressive multifocal leukoencephalopathy\n- Patients with unresolved bowel obstruction, including patients with radiological findings indicating bowel obstruction on diagnostic imaging\n- Chronic skin condition that requires systemic therapy"}

Primary endpoints

• {"endpoint_text":"- (Dose escalation and backfill) Occurrence of dose-limiting toxicities (DLTs) at different dose levels (during first treatment cycle of 3 weeks)","definition_or_measurement_approach":"DLTs assessed during first treatment cycle of 3 weeks at each dose level."}
• {"endpoint_text":"- (Dose escalation and backfill) Occurrence and severity of treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Occurrence and severity of TEAEs recorded (standard safety monitoring)."}
• {"endpoint_text":"- (Dose Optimization) ORR, disease control rate (DCR) and DoR according to RECIST v1.1 assessed by INV at futility analysis and in addition by blinded independent central review (BICR) at final study analysis","definition_or_measurement_approach":"Response assessments per RECIST v1.1 by Investigator at futility analysis and by BICR at final analysis to determine ORR, DCR and DoR."}
• {"endpoint_text":"- (Dose Optimization) Occurrence of TEAEs and treatment-related AEs (TRAEs)","definition_or_measurement_approach":"Recording incidence of TEAEs and TRAEs during dose optimization period."}
• {"endpoint_text":"- (Dose Optimization) Incidence and severity of TEAEs and TRAEs","definition_or_measurement_approach":"Incidence and severity grading of TEAEs and TRAEs using standard AE grading (e.g. CTCAE)."}

Secondary endpoints

• {"endpoint_text":"- (Dose escalation and backfill) In addition to safety (TEAE) and tolerability, the pharmacokinetics (PK) profile and preliminary clinical activity will be considered to determine the dose for optimization","definition_or_measurement_approach":"PK profiling and preliminary clinical activity combined with safety to select dose for optimization."}
• {"endpoint_text":"- (Dose escalation and backfill) PK parameters of TUB-030, total mAb and free exatecan, including Cmax, Cmin, Tmax and as far as collected data allow an estimation of t1/2, and area under the curve (AUC)","definition_or_measurement_approach":"Measurement of PK parameters (Cmax, Cmin, Tmax, t1/2 estimate, AUC) for conjugated ADC, total antibody and free exatecan."}
• {"endpoint_text":"- (Dose escalation and backfill) Incidence and semiquantitative titers of anti-drug antibodies (ADA) against TUB-030","definition_or_measurement_approach":"Assessment of ADA incidence and semi-quantitative titers against TUB-030."}
• {"endpoint_text":"- (Dose escalation and backfill) Objective response rate (ORR) by RECIST v1.1 assessed by Investigator (INV)","definition_or_measurement_approach":"ORR assessed per RECIST v1.1 by Investigator."}
• {"endpoint_text":"- (Dose escalation and backfill) Disease control rate (DCR) assessed by INV","definition_or_measurement_approach":"DCR assessed by Investigator."}
• {"endpoint_text":"- (Dose escalation and backfill) Duration of response (DoR) by RECIST v1.1 assessed by INV","definition_or_measurement_approach":"DoR per RECIST v1.1 assessed by Investigator."}
• {"endpoint_text":"- (Dose escalation and backfill) Progression-free survival (PFS) by RECIST v1.1 assessed by INV","definition_or_measurement_approach":"PFS measured per RECIST v1.1 by Investigator."}
• {"endpoint_text":"- (Dose escalation and backfill) Incidence of serious adverse events (SAEs)","definition_or_measurement_approach":"Recording and reporting of SAEs per standard regulatory requirements."}
• {"endpoint_text":"- (Dose escalation and backfill) Incidence of ≥grade 3 laboratory abnormalities","definition_or_measurement_approach":"Laboratory monitoring for grade ≥3 abnormalities using standard lab grading criteria."}
• {"endpoint_text":"- (Dose Optimization) PFS by RECIST v1.1 as assessed by INV at futility and at final study analysis and in addition retrospectively by BICR at final analysis","definition_or_measurement_approach":"PFS per RECIST v1.1 assessed by Investigator at futility and final analyses; retrospective BICR at final analysis."}
• {"endpoint_text":"- (Dose Optimization) OS by RECIST v1.1 as assessed by INV and retrospectively by BICR at final analysis","definition_or_measurement_approach":"Overall survival assessed by Investigator and retrospectively by BICR at final analysis."}
• {"endpoint_text":"- (Dose Optimization) Incidence of SAEs","definition_or_measurement_approach":"Recording incidence of SAEs during dose optimization."}
• {"endpoint_text":"- (Dose Optimization) Incidence of ≥grade 3 laboratory abnormalities","definition_or_measurement_approach":"Laboratory monitoring for grade ≥3 abnormalities during dose optimization."}

France

Earliest CTIS Part Ii Submission Date

20-10-2025

Latest Decision Or Authorization Date

03-11-2025

Processing Time Days

14

Number Of Sites

2

Number Of Participants

30

Spain

Earliest CTIS Part Ii Submission Date

14-10-2025

Latest Decision Or Authorization Date

05-11-2025

Processing Time Days

22

Number Of Sites

2

Number Of Participants

30

Romania

Earliest CTIS Part Ii Submission Date

07-10-2025

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

34

Number Of Sites

2

Number Of Participants

30

Primary sponsor

Full Name

Tubulis GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Icon (Lr) Limited

Responsibilities

collect and hold for imaging, independent reads in optimisation and ECGs collections

Name

Alira Health GmbH

Responsibilities

Operational and study support duties (codes: 1;10;14;2;5;6) as listed in sponsor duties

Third parties

• {"country":"Romania","full_name":"Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca","duties_or_roles":"investigator; 2","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"collect and hold for imaging, independent reads in optimisation and ECGs collections","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Italy","full_name":"Arithmos S.r.l.","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Institutul Oncologic Prof. Dr. Alexandru Trestioreanu Bucuresti","duties_or_roles":"investigator; 2","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Alira Health GmbH","duties_or_roles":"1; 10; 14; 2; 5; 6","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Lyo-X AG","duties_or_roles":"10; 4","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Swiss BioQuant AG","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}