ALE.P03 for Advanced or Metastatic Solid Tumors

Inclusion criteria

• {"criterion_text":"- Be voluntarily willing and able to provide written informed consent for the clinical study.\n- Male patients should agree to use an adequate method of contraception and to abstain from sperm donation starting with the first dose of study intervention through 90 days after the last dose of study intervention.\n- Be at least 18 years of age on the day of signing informed consent.\n- Have disease and treatment history as outlined below: • Have histologically or cytologically confirmed advanced locally recurrent and inoperable or metastatic CRC, iCCA, sqNSCLC, UC, or CSCC. • Have documented radiological disease progression at study entry. • Have adequate CLDN1 protein expression level as determined by a central laboratory: o For dedicated CLDN1+ backfilling cohorts in Phase I dose escalation, ≥ 75% of the tumor cells with CLDN1 protein expression of +2/+3, unless a different cut-off is recommended by the SRC. o For Phase I RDE part, ≥ 75% of the tumor cells with CLDN1 protein expression of +2/+3, unless a different cut-off is recommended by the SRC. o For Phase II part, ≥ 50% of the tumor cells with CLDN1 protein expression of +2/+3, unless a different cut-off is recommended by the SRC. • Phase I Dose Escalation: Have received the available systemic SOCs given in the advanced setting including an anti-PD-1/L1 monoclonal antibody (unless contraindicated) sequential or concurrent with chemotherapy and being refractory or intolerant to the treatment Phase I RDE and Phase II: o SqNSCLC: Have received one or two available systemic SOC regimens given in the advanced setting including an anti-PD-1/L1 monoclonal antibody (sequential or concurrent with cisplatin/carboplatin plus taxane) and being refractory or intolerant to the treatment. o iCCA: Have received one or two available systemic SOC regimens given in the advanced setting including an anti-PD-1/L1 monoclonal antibody (unless not reimbursed) and being refractory or intolerant to the treatment. o CRC: Have received at least two available systemic SOC regimens given in the advanced setting and being refractory or intolerant to the treatment. The following therapies might be included in prior lines of therapy:  Fluoropyrimidine, oxaliplatin, and/or irinotecan, anti-vascular endothelial growth factor, anti-EGFR unless contraindicated.  Anti-PD-1/L1 monoclonal antibody, if tumor is MSI-H/dMMR, or TMB-high, if clinically indicated and available. The corresponding targeted therapy for patients with known actionable alterations (e.g., HER2, KRAS G12C, BRAF V600E). o UC: Have received one or two available systemic SOC regimens given in the advanced setting including an anti-PD-1/L1 monoclonal antibody, EV, and being refractory or intolerant to the treatment. o CSCC: Have received one or two available SOC regimens given in the advanced setting including an anti-PD-1/L1 monoclonal antibody (for whose tumors express PD-L1 with Combined Positive Score ≥ 1), cisplatin/carboplatin plus taxane, TV and being refractory or intolerant to the treatment. Bevacizumab might be included in the SOC regimen as per local institutional guidelines. Applicable for Phase I Dose Escalation, Phase I RDE and Phase II: o Note 1: For patients with known actionable oncogenic drivers, they should have received the corresponding targeted therapy as deemed feasible. o Note 2: The availability of SOC should follow local institutional guidelines.\n- Have provided tissue for CLDN1 analysis in a central laboratory. Tumor tissue collection is mandatory at baseline (i.e., within 180 days prior to study enrollment) unless the biopsy procedure is considered a high risk for the patient’s safety as per the Investigator and local guidelines. In case the biopsy is not available, or the procedure is deemed unsafe, an archival tumor tissue sample older than 180 days can be submitted. However, preferably, this sample should have been collected no later than the start of the most recent previous anti-cancer treatment.\n- Have measurable disease based on RECIST 1.1, as determined by the site. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions occurring after termination of the most recent anti-cancer regimen prior to study entry.\n- Have a performance status of 0 or 1 on the ECOG PS.\n- Demonstrate adequate bone marrow and organ function as defined in Table 5–1. All screening laboratory assessments should be performed within 14 days of study intervention initiation. Patients must not have received red blood cell or platelet transfusion or growth factor support within 1 week prior to screening assessment.\n- Female patients of childbearing potential should have a negative blood pregnancy test within 72 hours prior to receiving the first dose of study intervention. A urine test can be considered if a blood test is not appropriate.\n- Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study intervention. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year."}

Exclusion criteria

• {"criterion_text":"- SqNSCLC and CSCC: diagnosed with a tumor of predominantly non-squamous histology result (e.g., adenosquamous carcinoma) or adenocarcinoma.\n- Has a history of (non-infectious) ILD/pneumonitis that required steroids or current symptomatic or clinically significant pneumonitis requiring steroids and/or immunosuppressive therapies.\n- For sqNSCLC patients: Has received radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study intervention.\n- Has clinically significant gastrointestinal bleeding (NCI CTCAE version 5.0 Grade 3 or higher) within 30 days prior to start of screening.\n- Has an active infection requiring systemic treatment (e.g., IV antibiotics, antivirals, or antifungals).\n- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the clinical study, interfere with the patient’s participation for the full duration of the clinical study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.\n- Is pregnant, breastfeeding, or expecting to conceive within the projected duration of the clinical study, starting with the screening visit through 180 days after the last dose of study intervention or father children starting with the screening visit through 90 days after the last dose of study intervention.\n- Has untreated chronic hepatitis B or is a chronic HBV carrier with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) at screening. Note: Inactive HBsAg carriers, treated patients, and patients with stable hepatitis B (HBV DNA < 500 IU/mL or < 2500 copies/mL) can be enrolled. Patients with detectable HBsAg or detectable HBV DNA should be managed per institutional treatment guidelines.\n- Has active HCV. Note: Patients with a negative HCV antibody test at screening or positive HCV antibody test followed by a negative HCV ribonucleic acid test at screening are eligible.\n- Has untreated HIV infection, if known. Patients with known HIV infection are eligible if the following criteria are met: • Stable on antiretroviral therapy for ≥ 4 weeks before first dose of study intervention. • Patient agrees to adhere to antiretroviral therapy per WHO guidelines. • No documented multidrug resistance that would prevent effective antiretroviral therapy. • Viral load of < 400 copies/mL at screening. • CD4+ T-cell count ≥ 350 cells/µL at screening. • No history of an acquired immunodeficiency syndrome-defining opportunistic infection ≤ 2 months before first dose of study intervention unless eligibility is agreed to by the Medical Monitor after consultation. • If prophylactic antimicrobial drugs are indicated, patients may still be eligible upon agreement with the Medical Monitor.\n- Has received a live vaccine within 30 days of planned start of study intervention.\n- Has received antineoplastic therapies prior to study intervention within specified time frame defined as follows: • Radiation therapy (or other non-systemic therapy) within 2 weeks prior to first dose of ALE.P03. Note: Palliative radiotherapy in a limited field is allowed. • Any other chemotherapy, immunotherapy (except for anti-PD-1/L1 defined as follows) or anti-cancer agents within 4 weeks or 5 times t1/2 of the first dose of ALE.P03, whichever is longer. • Anti-PD-1 Q2W/Q3W dose regimen (e.g., pembrolizumab 200 mg) or anti-PD-L1 Q3W/Q4W dose regimen (e.g., durvalumab 1,500 mg, pembrolizumab, nivolumab) within 60 days of the first dose of ALE.P03. • Anti-PD-1/L1 Q4W/Q6W dose regimen (e.g., pembrolizumab 400 mg, durvalumab, nivolumab) within 120 days of the first dose of ALE.P03. • Investigational therapy within 4 weeks of the first dose of ALE.P03 (Note: Participation in the follow-up phase, i.e., receiving no study intervention, of a prior study is allowed). • Has not fully recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to a previously administered treatment. Note: Patients with ≤ Grade 2 neuropathy, ≤ Grade 2 alopecia, or laboratory values within those specified in Table 5–1, are an exception to this criterion and may qualify for the study after discussion with the Medical Monitor. • If patients underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.\n- Has received previous ADC treatment with Topo-I payload.\n- Has received previous CLDN1 targeted therapy.\n- Has known hypersensitivity to the study intervention or any of the excipients used in the formulation of the study intervention.\n- Patients taking CYP1A2 substrates with a narrow therapeutic index (such as theophylline, tacrine, clozapine, olanzapine, and R-warfarin) (except for caffeine) that cannot be discontinued during the study intervention through 3 weeks after the last dose of ALE.P03.\n- Patients with active keratitis or corneal ulcerations. Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the Investigator.\n- Has known homozygous status for the UGT1A1*28 allele.\n- Has rapidly progressing disease in the opinion of the treating Investigator or designee, as evidenced by one or more of the following: • Uncontrolled tumor pain (e.g., pain > 6 on the EVA scale). • Condition requiring urgent medical treatment. • Undergoing evaluation for oncologic medical emergencies. • Advanced, symptomatic, visceral spread with risk of short -term life-threatening complications, including organ compromise and/or uncontrolled effusions (pleural, pericardial, peritoneal) requiring repeated drainage.\n- Has a diagnosed and/or treated additional second malignancy within 3 years prior to C1D1 except for: curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively resected in situ cervical cancer (not applicable for patients enrolled with CSCC), and curatively resected in situ breast cancer. Other exceptions may be considered with the Medical Monitor or designee consultation.\n- Any of the following cardiac criteria: • Mean resting QTcF > 470 milliseconds obtained from triplicate ECGs. • Any factors that increase the risk of QT prolongation, shortening or risk of arrhythmic events such as hypokalemia, congenital long or short QT syndrome, family history of long QT syndrome, familial short QT syndrome, or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong or shorten the QT interval (see Appendix 8, Section 10.8). • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, second-or third-degree atrioventricular block, and clinically significant sinus node dysfunction not treated with pacemaker.\n- Has known active CNS metastases and/or carcinomatous meningitis. Note: Patients with previously treated CNS metastases may participate provided they have received prior local therapy (e.g., surgery, stereotactic radiosurgery or whole brain radiotherapy) and are stable (without evidence of progression by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of ALE.P03 and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging CNS metastases, and are not using steroids for at least 7 days prior to start of ALE.P03. This exception does not include leptomeningeal disease which is excluded regardless of clinical stability.\n- Has had an allogeneic tissue/solid organ transplant."}

Primary endpoints

• {"endpoint_text":"- Phase 1: Incidence of DLTs","definition_or_measurement_approach":"Incidence of dose-limiting toxicities (DLTs) during Phase 1 dose escalation (as stated)."}
• {"endpoint_text":"- Phase 1: Incidence and severity of AEs and SAEs","definition_or_measurement_approach":"Incidence and severity (reporting) of adverse events (AEs) and serious adverse events (SAEs) as collected during Phase 1."}
• {"endpoint_text":"- Phase 1: Clinically significant changes in laboratory values, vital signs, and ECGs","definition_or_measurement_approach":"Assessment of clinically significant changes in laboratory values, vital signs and ECG recordings during Phase 1."}
• {"endpoint_text":"- Phase 1: Tolerability: dose interruptions and dose intensity","definition_or_measurement_approach":"Tolerability assessed by recording dose interruptions and dose intensity during Phase 1."}
• {"endpoint_text":"- Phase 1: Preliminary efficacy parameters per RECIST 1.1 (see protocol for further details): o ORR (defined as CR rate + PR rate) o DoR Note: CLDN1 expression and tumor type subgroup analyses may be performed for these endpoints.","definition_or_measurement_approach":"Efficacy assessed per RECIST 1.1: objective response rate (ORR = CR + PR) and duration of response (DoR); subgroup analyses by CLDN1 expression and tumor type may be performed."}
• {"endpoint_text":"- Phase 2: Efficacy parameters per RECIST 1.1*: • ORR • DoR Note: CLDN1 expression and tumor type subgroup analyses may be performed for these endpoints.","definition_or_measurement_approach":"Efficacy in Phase 2 assessed per RECIST 1.1: ORR and DoR; subgroup analyses by CLDN1 expression and tumor type may be performed."}

Secondary endpoints

• {"endpoint_text":"- Incidence and severity of AEs and SAEs","definition_or_measurement_approach":"Incidence and severity of adverse events and serious adverse events as recorded during the study."}
• {"endpoint_text":"- Clinically significant changes in laboratory values, vital signs, and ECGs","definition_or_measurement_approach":"Monitoring for clinically significant changes in laboratory values, vital signs and ECGs."}
• {"endpoint_text":"- Tolerability: dose interruptions and dose intensity","definition_or_measurement_approach":"Assessment of dose interruptions and dose intensity across study phases."}
• {"endpoint_text":"- DCR per RECIST 1.1 (see protocol for further details)","definition_or_measurement_approach":"Disease control rate assessed per RECIST 1.1."}
• {"endpoint_text":"- Median PFS (and rate at 6 and 12 months) per RECIST 1.1 (see protocol for further details)","definition_or_measurement_approach":"Progression-free survival (median and rates at 6 and 12 months) assessed per RECIST 1.1."}
• {"endpoint_text":"- Median OS and rate of 6-, 12-, and 24-month survival Note: CLDN1 expression and tumor type subgroup analyses may be performed for these endpoints.","definition_or_measurement_approach":"Overall survival (median and survival rates at 6, 12, and 24 months); subgroup analyses by CLDN1 expression and tumor type may be performed."}
• {"endpoint_text":"- PK: • Plasma concentration of ALE.P03 ADC (including total antibody, conjugated exatecan, and free payload exatecan) by cohort PK parameters including, but not limited to, AUCtau, AUClast, AUC0-inf, Cmax, Cmin, Ctrough, Kel, t½, tmax, Cavg, and other parameters as appropriate for total antibody, conjugated exatecan, and free payload exatecan for each dose level and cycle as supported by available data","definition_or_measurement_approach":"Pharmacokinetics: plasma concentrations and PK parameters (AUCtau, AUClast, AUC0-inf, Cmax, Cmin, Ctrough, Kel, t½, tmax, Cavg, etc.) for total antibody, conjugated exatecan, and free exatecan per cohort/dose level."}
• {"endpoint_text":"- Immunogenicity: • Presence of anti-ALE.P03 antibodies with screening and confirmatory assay, as appropriate • Proportion of patients categorized by ADA status (ADA positive/negative) following confirmatory assay","definition_or_measurement_approach":"Immunogenicity assessed by screening and confirmatory anti-ALE.P03 antibody assays; reporting proportion ADA positive vs negative."}

France

Earliest CTIS Part Ii Submission Date

13-10-2025

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

31

Number Of Sites

5

Number Of Participants

16

Italy

Earliest CTIS Part Ii Submission Date

14-10-2025

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

30

Number Of Sites

7

Number Of Participants

26

Spain

Earliest CTIS Part Ii Submission Date

13-10-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

35

Number Of Sites

12

Number Of Participants

30

Netherlands

Earliest CTIS Part Ii Submission Date

14-10-2025

Latest Decision Or Authorization Date

12-11-2025

Processing Time Days

29

Number Of Sites

3

Number Of Participants

5

Primary sponsor

Full Name

Alentis Therapeutics AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Parexel International Limited

Responsibilities

sponsorDuties codes: [11,5]

Name

Medidata Solutions Inc.

Responsibilities

RTSM, Central Imaging

Name

Charles River Laboratories Evreux

Responsibilities

sponsorDuties codes: [4]

Name

Discovery Life Sciences LLC

Responsibilities

sponsorDuties codes: [4]

Name

Bioagilytix Labs LLC

Responsibilities

sponsorDuties codes: [4]

Name

Fisher Clinical Services GmbH

Responsibilities

sponsorDuties codes: [14]

Third parties

• {"country":"France","full_name":"Charles River Laboratories Evreux","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Discovery Life Sciences LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"RTSM, Central Imaging (sponsorDuties code: 15)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC (San Diego address)","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Parexel International Limited","duties_or_roles":"sponsorDuties codes: [11,5]","organisation_type":"Pharmaceutical company"}