A Study to Investigate ALE.P02 as Monotherapy or in Combination with Pembrolizumab in Adult Patients with Selected CLDN1+ Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alentis Therapeutics AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 May 2025 → ongoing

Decision date (initial)

2025-04-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Alentis Therapeutics AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Efficacy, Pharmacokinetic, Safety

To evaluate safety and tolerability of ALE.P02 as monotherapy or in combination with pembrolizumab (Phase I Monotherapy and Combination Dose Escalation).
To establish RP2D for ALE.P02 (Phase I Monotherapy RDE).
To establish a recommended dose for future development of ALE.P02 in combination with pembrolizumab (Phase I Combination Dose Expansion)
To assess anti-tumor activity of ALE.P02 monotherapy (Phase II Monotherapy)

Secondary objectives 4

1. Preliminary evidence of anti-tumor activity of ALE.P02 as monotherapy or in combination with pembrolizumab
2. To assess the pharmacokinetic (PK) profile of ALE.P02
3. To evaluate the immunogenicity of ALE.P02
4. To evaluate the safety and tolerability of ALE.P02 as monotherapy or in combination with pembrolizumab (Phase I Monotherapy and Combination Dose Expansion and Phase II Monotherapy)

Conditions and MedDRA coding

Advanced or Metastatic Squamous Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Be voluntarily willing and able to provide written informed consent for the clinical study.
2. Female patients of childbearing potential should have a negative blood pregnancy test within 72 hours prior to receiving the first dose of study treatment. A urine test can be considered if a blood test is not appropriate. Female patients of childbearing potential should be willing to use 2 methods of birth control (barrier method combined with one of the highly effective methods of birth control defined in Appendix 4, Section 10.4) or be surgically sterile or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study treatment. Female patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year. Male patients should agree to use an adequate method of contraception and to abstain from sperm donation starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred method of contraception for the patient.
3. Should be willing and able to comply with all protocol requirements.
4. Be at least 18 years of age on the day of signing informed consent.
5. Have disease and treatment history as outlined below: • Have histologically or cytologically confirmed advanced locally recurrent and inoperable or metastatic SqNSCLC, HNSCC (nasopharyngeal cancer included), ESCC, or CSCC. o For Monotherapy and Combination Phase I Expansion: ≥75% of the tumor cells with CLDN1 protein expression of +2/+3 unless different cut-off is agreed by SRC. o For Monotherapy Phase II: ≥50% of the tumor cells with CLDN1 protein expression of +2/+3, unless different cut-off is agreed by SRC. • Phase I Monotherapy Dose Escalation: Have received and are refractory or intolerant to the available systemic SoC regimens given in the advanced setting including an anti-PD-1/L1 monoclonal antibody (unless contraindicated), administered: o sequential or concurrent with chemotherapy, and/or o in combination with a monoclonal antibody or o as monotherapy (for patients with high PD-L1 expression, accordning to institutional guidelines). • Phase I Combination in metastatic HNSCC or SqNSCLC patients o Dose escalation: Have received and are refractory to at least one prior systemic therapy including an anti-PD-1/L1 mAb. o Dose expansion: Have received no previous systemic therapy administered in the incurable recurrent or metastatic setting and eligible to receive pembrolizumab as first-line monotherapy with tumor expression PD-L1 based on local institutional guidelines. • Phase I Monotherapy RDE and Phase II: o SqNSCLC: Have received one or two available systemic SoC regimen(s) given in the advanced setting including an anti-PD-1/L1 monoclonal antibody (sequential or concurrent with cisplatin/carboplatin plus taxane) and refractory or intolerant to the treatment. o HNSCC: Have received one or two available systemic SoC regimen(s) given in the advanced setting including an anti-PD-1/L1 monoclonal antibody (sequential or concurrent with cisplatin/carboplatin plus 5-fluorouracil [5-FU]) and refractory or intolerant to the treatment. Anti-epidermal growth factor receptor monoclonal antibody might be included in standard of care (SoC) regimen as per local institutional guidelines. o ESCC: Have received one or two available systemic SoC regimen(s) given in the advanced setting including an anti-PD-1/L1 monoclonal antibody (sequential or concurrent with capecitabine + oxaliplatin OR 5-FU + cisplatin/carboplatin OR other chemotherapy combination) as per local institutional guidelines. o CSCC: Have received one or two available systemic SoC regimen(s) 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 and refractory or intolerant to the treatment. Bevacizumab might be included in SoC regimen as per local institutional guidelines. Note 1: For patients with known actionable oncogenic drivers, they should have received the corresponding targeted therapy as deemed feasible. Note 2: The availability of SoC should follow local institutional guidelines. Note 1 and Note 2 are applicable to both Phase I monotherapy dose escalation and RDE/Phase II and to Phase I combination dose escalation and expansion.
6. Have provided tissue for CLDN1 analysis in a central laboratory. Fresh tumor tissue collection is mandatory at baseline, any sample taken within 180 days prior to Cycle 1 Day 1 is considered fresh. Only in the case that no sample taken within the last 180 days is available and no sample can be taken because the biopsy procedure is deemed unsafe by the treating investigator or designee, will an archival tumor tissue older than 180 days be accepted. Preferably, this sample should have been collected no later than the start of the most recent previous anti-cancer treatment.
7. Have measurable disease based on Response Evaluation Criteria in Solid Tumors (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.
8. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
9. Demonstrate adequate bone marrow and organ function. All screening laboratory assessments should be performed within 14 days of treatment initiation. Patients must not have received red blood cell or platelet transfusion, or growth factor support 1 week prior to screening assessment. Bone Marrow and Organ Function System Laboratory Value Hematologic Absolute neutrophil count ≥ 1,500/mm3(1.5 × 109/L) Platelets ≥75,000/mm3(75 × 109/L) Hemoglobin ≥9 g/dL (90 g/L) or ≥5.6 mmol/L Renal Measured or calculated creatinine clearance as per local institutional standard (eGFR can also be used in place of creatinine clearance) ≥50 mL/min Hepatic Total bilirubin ≤1.5 × ULN AST and ALT ≤3 × ULN Coagulation INR or PT ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants. Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; eGFR = estimated glomerular filtration rate; INR = international normalized ration; PT = prothrombin time; ULN = upper limit of normal
10. Patients must have recovered from all toxicities led by prior treatment (recover to < Grade 2 based on Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria, or to levels defined in the eligibility criteria) with the exception of toxicities not considered a safety risk (eg, alopecia, vitiligo, and other asymptomatic laboratory abnormalities). Patients with stable, well-controlled hypothyroidism using thyroid replacement therapy or patient with well-controlled adrenal insufficiency due to prior immunotherapy, are allowed. Corticosteroid replacement must not exceed physiological doses (must not exceed prednisone 10 mg/day or equivalent).

Exclusion criteria 32

1. Have been diagnosed with cancers of predominantly non-squamous histology (eg, adenosquamous carcinoma) or adenocarcinoma.
2. Have had an allogeneic tissue/solid organ transplant.
3. Have used of any drugs or herbal remedies known to be strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) for 14 days prior to dosing or 5 half-lives (whichever is longer) and throughout the study.
4. Have a history of (non-infectious) ILD/pneumonitis that required steroids or a current ILD/pneumonitis.
5. Have clinically significant gastrointestinal bleeding (National Cancer Institute [NCI] CTCAE version 5.0 Grade 3 or higher) within 30 days prior to start of screening. However, patients with feeding tubes or stents may be included.
6. Have an active infection requiring systemic treatment (eg, IV antibiotics, antivirals, or antifungals).
7. Have 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 or designee.
8. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with positive HBV deoxyribonucleic acid (DNA) at screening. Note: Inactive hepatitis B surface antigen carriers, treated patients, and patients with stable hepatitis B (HBV DNA <500 IU/mL or <2500 copies/mL) can be enrolled. Patients with positive hepatitis B surface antigen or positive HBV DNA should be managed per institutional treatment guidelines.
9. Have active hepatitis C. Note: Patients with a negative hepatitis C virus (HCV) antibody test at screening or positive HCV antibody test followed by a negative HCV ribonucleic acid test at screening are eligible.
10. Have untreated human immunodeficiency virus infection, if known. Patients with known human immunodeficiency virus infection are eligible if the following criteria are met: • Stable on antiretroviral therapy for ≥4 weeks before first dose of study treatment • Patient agrees to adhere to antiretroviral therapy per World Health Organization guidelines • No documented multidrug resistance that would prevent effective antiretroviral therapy. • Viral load of <400 copies per mL at screening • CD4+ T-cell count ≥350 cells per µL at screening • No history of an acquired immunodeficiency syndrome-defining opportunistic infection ≤ 2 months before first dose of study treatment 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.
11. Have received a live vaccine within 30 days of planned start of Cycle 1 Week 1 (Day 1).
12. Have received antineoplastic therapies prior to study treatment within specified time frame, defined as follows: • 2a Radiation therapy (or other non-systemic therapy) within 14 days prior to Cycle 1 Day 1 (Note: Palliative radiotherapy to a limited field is allowed) • 2b Investigational product within 28 days of Cycle 1 Day 1. • 2c. Chemotherapy, immunotherapy (other than anti-PD-1/L1 agents [see Exclusion Criterion 2d]), or other systemic agents within 28 days or 5 times half-life or Cycle 1 Day 1 of the treatment, whichever is shorter. • 2d. Prior anti-PD-1/ L1 treatment: o Phase I Monotherapy/Combination Dose Escalation, Dose Explansion and Phase II Monotherapy cohorts:  Q2W/Q3W dose regimen (eg Pembrolizumab 200 mg) within 60 days of Cycle 1 Day 1.  Every 4 weeks (Q4W)/every 6 weeks (Q6W) dose regimen (eg, pembrolizumab 400 mg) within 120 days of Cycle 1 Day 1. o Phase i Dose Escalation Anti-PD-1/L1 washout cohort only:  Anti-PD1/L1 within 28 days or more than 60 days of Cycle 1 Day 1. Exclusion Criterion 2d referring to prior anti-PD-1/L1 treatment may be removed upon agreement with the SRC after review of anti-PD-1/L1 agents will be adjusted to at least 28 days (per Exclusion Criterion 2c).
13. Have used concomitant drugs that are known to prolong or shorten QT and/or have known risk of Torsades de Pointes.
14. Have received prior ADC treatment with MMAE payload.
15. Have received prior CLDN1 targeted therapy.
16. For SqNSCLC patients: Have received radiation therapy to the lung with curative intent within 6 months of the first dose of study treatment.
17. Have undergone major surgery within 4 weeks prior Cycle 1 Day 1 and have not adequately recovered from surgery or its complications prior to starting study treatment.
18. Have 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.
19. Have rapidly progressing disease in the opinion of the treating Investigator or designee, eg, patients with uncontrolled tumor pain (eg, pain > 6 on the visual analogue scale [VAS] ), requiring urgent medical treatment, patients undergoing evaluation for oncologic medical emergencies and/or patients with advanced, symptomatic, visceral spread that are at risk of life-threatening complications in the short--term, including organ compromise and/or uncontrolled effusions (pleural, pericardial, peritoneal) requiring repeated drainage.
20. Have a diagnosed and/or treated additional second malignancy within 3 years prior to Cycle 1, Day 1 except for: curatively treated basal cell carcinoma of the skin, squamous solid tumor or cancer 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 in consultation with the Medical Monitor or designee.
21. Have uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥8% or HbA1c 7% to <8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
22. Have any of the following cardiac criteria: (a) Mean resting QTcF > 470 milliseconds. (b) 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. (c) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, complete left bundle branch block, second-or third-degree atrioventricular block, and clinically significant sinus node dysfunction not treated with pacemaker.
23. Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. (Note: Patients with previously treated CNS metastases may participate provided they have received prior local therapy (eg, surgery, stereotactic radiosurgery or whole brain radiotherapy), are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either magnetic resonance imaging (MRI) or computed tomography (CT) scan for at least 4 weeks prior to the first dose of study treatment 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 study treatment. This exception does not include leptomeningeal disease which is excluded regardless of clinical stability.
24. Have experienced treatment-related ≥ Grade 2 immune-mediated hepatitis during the prior anti-PD-1/L1 treatment.
25. Have experienced immune-related AEs leading to discontinuation of prior immune-oncology agents (including anti-PD-[L]1 or anti-cytotoxic T-lymphocyte associated protein-4) (Phase I Combination part only).
26. Patients who discontinued prior anti-cancer treatment or experienced dose reduction due to neuropathy.
27. Have received prior systemic treatment of microtubule inhibitors (eg, taxanes) given in the advanced setting (Phase I Monotherapy RDE and Phase II Monotherapy, HNSCC and ESCC only).
28. Have known hypersensitivity to the study treatment or any of the excipients used in the formulation of the study treatment.
29. Phase I Combination Dose Escalation and Expansion only: Have known hypersensitivity to pembrolizumab or its excipients.
30. Phase I Combination Dose Escalation and Expansion only: Systemic steroid therapy prednisone or prednisone >10 mg/day dose equivalent, or any other form of immunosuppressive therapy within 7 days or 5 half-lives, whichever is greater, prior to the first dose of the ALE.P02 and pembrolizumab combination therapy. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
31. Have active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
32. Are pregnant or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Incidence of DLTs
2. Incidence and severity of AEs, SAEs
3. Clinically significant changes in laboratory values, vital signs, and electrocardiograms
4. Tolerability: dose interruptions and dose intensity
5. Preliminary efficacy parameters per RECIST 1.1: • ORR defined as CR rate + PR rate • DoR: duration of response Note: CLDN1 and indication subgroup analysis will also be performed
6. ORR defined as CR rate + PR rate per RECIST 1.1
7. DoR: duration of response Note: CLDN1 and indication subgroup analysis will also be performed

Secondary endpoints 9

1. DCR defined as CR rate + PR rate + SD rate per RECIST 1.1
2. Median PFS (and rate at 6 and 12 months) per RECIST 1.1
3. Median OS and rate of 6-month, 12-month, and 24-month survival
4. Blood concentration: concentration of ALE.P02 ADC, total antibody and MMAE (payload)
5. PK parameters including, but not limited to AUCtau, AUClast, AUCinf, Cmax, Cmin, Ctrough, Kel, t ½, Tmax, Cavg and other parameters as appropriate for ALE.P02 ADC, total antibody and MMAE
6. Presence of anti-ALE.P02 antibodies with screening and confirmatory assay, as appropriate
7. Incidence and severity of AEs and SAEs
8. Clinically significant changes in laboratory values, vital signs, and electrocardiograms
9. Tolerability: dose interruptions and dose intensity

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alentis Therapeutics AG

Sponsor organisation

Alentis Therapeutics AG

Address

Hegenheimermattweg 167a

City

Allschwil

Postcode

4123

Country

Switzerland

Scientific contact point

Organisation

Alentis Therapeutics AG

Contact name

Clinical Trial Manager

Public contact point

Organisation

Alentis Therapeutics AG

Contact name

Clinical Trial Manager

Third parties 9

Locations

3 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications