Clinical Trials List
Protocol NumberALP102CT
Active
2025-09-01 - 2028-09-30
Phase I
Recruiting5
ICD-10A00.0
Cholera due to Vibrio cholerae 01, biovar cholerae
ICD-9001.0
Cholera due to Vibrio cholerae
An open-label, multicenter, phase I trial was conducted to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ALPS12 in patients with metastatic small cell lung cancer.
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Trial Applicant
Chugai Pharma Taiwan Ltd.
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Sponsor
Taiwan Chung Wai Pharmaceutical Co., Ltd.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/07/22
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yuh-Min Chen 無
- 蕭慈慧 無
- Yung-Hung Luo 無
- Hsu-ching Huang 無
- 趙恒勝 無
- 廖映庭 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wu-Chou Su Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Seu-Chun Yang Division of General Internal Medicine
- Po-Lan Su Division of General Internal Medicine
- Chun-Hui Lee Division of Hematology & Oncology
- Chin-Wei Kuo Division of General Internal Medicine
- 蔡政軒 Division of General Internal Medicine
- Chian-Wei Chen Division of General Internal Medicine
- 林建佑 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- TSUNG -YING YANG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- YEN-HSIANG HUANG Division of Thoracic Medicine
- 李柏昕 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Cheng-Ta Yang
Co-Principal Investigator
- 柯皓文
- Chien-Ying Liu
- Fu-Tsai Chung
- Chih-Liang Wang
- 林定佑 Division of Hematology & Oncology
- 吳教恩 Division of Hematology & Oncology
- Shih-Hong Li Division of Hematology & Oncology
- 邱立忠
- 枋岳甫 Division of Hematology & Oncology
- Chih-Hsi Kuo
- 黃宗楨
- Chih-Hung Chen
- 吳浩銘
- 徐禀智
- 黃世緯
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Part 1: Dose Escalation Section ⚫ Incidence, nature, and severity of adverse events (AEs) (according to NCI CTCAE v.5.0 grading), CRS and immune effector cell-related neurotoxic syndromes (ICANS) are graded according to the ASTCT consensus grading criteria. ⚫ Nature and frequency of dose-limiting toxicities (DLT), AEs, PK, and pharmacodynamic properties. ⚫ Serum ALPS12 concentrations and their PK parameters, including maximum serum concentration (Cmax) and area under the plasma concentration-time curve (AUC). ⚫ Incidence of ALPS12 anti-antibody (ADA) and its impact on ALPS12 exposure. Part 2: Extended Section ⚫ Objective response, defined as a confirmed complete response (CR) or partial response (PR) conforming to RECIST v.1.1, as determined by the trial administrator. ⚫ Incidence, nature, and severity of AEs (according to NCI CTCAE v.5.0 grading), CRS and ICANS are graded according to the ASTCT consensus grading criteria. Consensus grading standard grading
Objectives
Main Objectives
Part 1: Dose Escalation
⚫Evaluate the safety and tolerability of ALPS12 combined with obinutuzumab as pre-treatment
⚫Determine the maximum tolerated dose (MTD) and/or recommended dose (RD) for the extension phase, and the dosing regimen for ALPS12 combined with obinutuzumab as pre-treatment
⚫Evaluate the pharmacokinetic (PK) characteristics of ALPS12 combined with obinutuzumab as pre-treatment
⚫Investigate the immunogenicity of ALPS12 combined with obinutuzumab as pre-treatment
Part 2: Extension
⚫Evaluate the preliminary antitumor activity of different doses of ALPS12 combined with obinutuzumab as pre-treatment, determined by tumor assessment, in patients with metastatic small cell lung cancer (SCLC)
⚫Evaluate the safety and tolerability of different doses of ALPS12 combined with obinutuzumab as pre-treatment
⚫Determine the maximum tolerated dose (MTD) and/or recommended dose (RD) for ALPS12 combined with obinutuzumab as pre-treatment Recommended dose (RP2D) and dosing regimen for the second phase of pre-treatment.
Test Drug
ALPS12
Gazyva
Gazyva
Active Ingredient
ALPS12
1013004400
1013004400
Dosage Form
Injectable solutions
Injectable solutions
Injectable solutions
Dosage
80mg/ml
1000 mg/40 mL (25 mg/mL)
1000 mg/40 mL (25 mg/mL)
Endpoints
Part 1: Dose Escalation Section
⚫Incidence, nature, and severity of adverse events (AEs) (according to NCI CTCAE v.5.0 classification), CRS and immune effector cell-related neurotoxic syndromes (ICANS) are classified according to the ASTCT consensus grading criteria.
⚫Nature and frequency of dose-limiting toxicities (DLTs), AEs, PKs, and pharmacodynamic properties.
⚫Serious ALPS12 concentrations and their PK parameters, including maximum serum concentration (Cmax) and area under the plasma concentration-time curve (AUC).
⚫Incidence of ALPS12 anti-antibody (ADA) and its impact on ALPS12 exposure.
Part 2: Extended Section
⚫Objective response, defined as a confirmed complete response (CR) or partial response (PR) conforming to RECIST v.1.1, as determined by the trial administrator.
⚫Incidence, nature, and severity of AEs (according to NCI CTCAE v.5.0 classification), CRS and ICANS. Then classify according to the ASTCT consensus classification standard.
⚫Incidence, nature, and severity of adverse events (AEs) (according to NCI CTCAE v.5.0 classification), CRS and immune effector cell-related neurotoxic syndromes (ICANS) are classified according to the ASTCT consensus grading criteria.
⚫Nature and frequency of dose-limiting toxicities (DLTs), AEs, PKs, and pharmacodynamic properties.
⚫Serious ALPS12 concentrations and their PK parameters, including maximum serum concentration (Cmax) and area under the plasma concentration-time curve (AUC).
⚫Incidence of ALPS12 anti-antibody (ADA) and its impact on ALPS12 exposure.
Part 2: Extended Section
⚫Objective response, defined as a confirmed complete response (CR) or partial response (PR) conforming to RECIST v.1.1, as determined by the trial administrator.
⚫Incidence, nature, and severity of AEs (according to NCI CTCAE v.5.0 classification), CRS and ICANS. Then classify according to the ASTCT consensus classification standard.
Inclution Criteria
Inclusion Criteria
Patients must meet the following inclusion criteria:
ECOG performance status of 0 or 1 (see Appendix 7).
Life expectancy of at least 12 weeks.
Histologically confirmed metastatic SCLC with recurrence after at least one systemic therapy. If the patient has available approved standard of care, the trial administrator must discuss the risks and benefits of alternative therapy with the patient before obtaining informed consent for this trial. The discussion must be documented in the patient's record.
Representative sealed tumor specimens must be available, either formalin-fixed, paraffin-embedded (FFPE) tissue blocks, or ≥ 8 unstained sections.
Acceptable sealed specimens:
Preferably sealed specimens within 12 months.
If suitable tissues are available at different time points (e.g., at initial diagnosis and at disease recurrence) and/or from multiple metastatic tumors, the most recent tissue is preferred (preferably specimens following recent systemic therapy). Depending on availability, multiple specimens may be collected from the patient; however, a single tissue section or excised specimen should meet the requirements of a paraffin-embedded tissue block or at least six unstained sections.
The patient has measurable lesions that meet RECIST v.1.1 criteria.
Adequate hematological and distal organ function, defined by laboratory test results obtained within 14 days prior to COD1, as follows:
Absolute neutrophil count (ANC) ≥ 1,500 cells/μL.
Lymphocyte count ≥ 500/μL.
Platelet count ≥ 100,000/μL (no transfusion within 14 days prior to COD1).
Hemoglobin ≥ 9.0 g/dL.
▪ The patient can receive transfusions or erythropoietin therapy according to local standard treatment.
Total bilirubin ≤ 1.5 times ULN.
▪ Total bilirubin in patients with Gilbert’s syndrome may be ≤ 3.0 times the ULN.
ALT and AST ≤ 2.5 times the ULN.
▪ ALT/AST in patients with a history of liver metastases may be ≤ 3.0 times the ULN.
Alkaline phosphatase (ALP) ≤ 2.5 times the ULN, except in the following cases:
▪ ALP in patients with a history of liver or bone metastases may be ≤ 5.0 times the ULN.
Serum albumin ≥ 2.5 g/dL.
PT and aPTT ≤ 1.5 times the ULN (applicable only to patients not receiving anticoagulation therapy; patients receiving anticoagulation therapy should maintain a stable dose).
Creatinine clearance ≥ 60 mL/min, measured or calculated according to the Cockcroft-Gault glomerular filtration rate formula:
(140 - age) × (kg body weight) × (0.85, for females) /
72 × (serum creatinine mg/dL)
Patients must meet the following inclusion criteria:
ECOG performance status of 0 or 1 (see Appendix 7).
Life expectancy of at least 12 weeks.
Histologically confirmed metastatic SCLC with recurrence after at least one systemic therapy. If the patient has available approved standard of care, the trial administrator must discuss the risks and benefits of alternative therapy with the patient before obtaining informed consent for this trial. The discussion must be documented in the patient's record.
Representative sealed tumor specimens must be available, either formalin-fixed, paraffin-embedded (FFPE) tissue blocks, or ≥ 8 unstained sections.
Acceptable sealed specimens:
Preferably sealed specimens within 12 months.
If suitable tissues are available at different time points (e.g., at initial diagnosis and at disease recurrence) and/or from multiple metastatic tumors, the most recent tissue is preferred (preferably specimens following recent systemic therapy). Depending on availability, multiple specimens may be collected from the patient; however, a single tissue section or excised specimen should meet the requirements of a paraffin-embedded tissue block or at least six unstained sections.
The patient has measurable lesions that meet RECIST v.1.1 criteria.
Adequate hematological and distal organ function, defined by laboratory test results obtained within 14 days prior to COD1, as follows:
Absolute neutrophil count (ANC) ≥ 1,500 cells/μL.
Lymphocyte count ≥ 500/μL.
Platelet count ≥ 100,000/μL (no transfusion within 14 days prior to COD1).
Hemoglobin ≥ 9.0 g/dL.
▪ The patient can receive transfusions or erythropoietin therapy according to local standard treatment.
Total bilirubin ≤ 1.5 times ULN.
▪ Total bilirubin in patients with Gilbert’s syndrome may be ≤ 3.0 times the ULN.
ALT and AST ≤ 2.5 times the ULN.
▪ ALT/AST in patients with a history of liver metastases may be ≤ 3.0 times the ULN.
Alkaline phosphatase (ALP) ≤ 2.5 times the ULN, except in the following cases:
▪ ALP in patients with a history of liver or bone metastases may be ≤ 5.0 times the ULN.
Serum albumin ≥ 2.5 g/dL.
PT and aPTT ≤ 1.5 times the ULN (applicable only to patients not receiving anticoagulation therapy; patients receiving anticoagulation therapy should maintain a stable dose).
Creatinine clearance ≥ 60 mL/min, measured or calculated according to the Cockcroft-Gault glomerular filtration rate formula:
(140 - age) × (kg body weight) × (0.85, for females) /
72 × (serum creatinine mg/dL)
Exclusion Criteria
Poorly controlled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), unstable angina, New York Heart Association grade II or higher congestive heart failure (see Appendix 6), serious arrhythmias requiring treatment (excluding atrial fibrillation and paroxysmal supraventricular tachycardia), or a history of myocardial infarction within 6 months of COD1.
Poorly controlled type 2 diabetes, defined as HbA1c ≥ 8% or fasting blood glucose ≥ 160 mg/dL (or 8.8 mmol/L) at screening.
Clinically significant major surgery or traumatic injury within 28 days prior to COD1 (as determined by the trial administrator), or anticipated major surgery during the trial.
Patients with a history of malignant tumors but with an extremely low risk of metastasis or death (e.g., appropriately treated cervical carcinoma in situ, basal cell carcinoma of the skin, localized prostate cancer, ductal carcinoma in situ of the breast, or cured resection of thyroid cancer with good histological condition) are eligible for inclusion.
Patients with malignant tumors who have received radical treatment and have been in tumor remission for ≥ 2 years prior to the first ALPS12 infusion without further treatment are also eligible for inclusion.
Patients must have received other investigational treatment within 21 days prior to starting C0D1.
QT interval (QTcF) corrected according to the Fridericia formula > 470 ms. Abnormal electrocardiogram findings (repeated three times, with intervals > 30 minutes).
A history of ventricular arrhythmias or risk factors for ventricular arrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary artery disease (with symptoms or confirmed by diagnostic tests as focal ischemia), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or a family history of unexplained sudden death or QT prolongation syndrome.
Current drug treatment is known to prolong the QT interval.
Previous treatment with anti-CD137 drugs, anti-CD3 drugs, and/or DLL3 targeted therapy.
The patient must have received anticancer therapy, whether investigational or approved, including chemotherapy, hormone therapy, and/or radiation therapy, within 21 days prior to the initiation of the first ALPS12 infusion, except in the following cases:
* Prior cancer vaccine and/or cytokine therapy, provided that at least 4 weeks or 5 drug half-lives (whichever is shorter) separate the last dose of the prior therapy from the first ALPS12 infusion.
* Received prostate cancer GnRH agonist or antagonist hormone therapy.
* Hormone replacement therapy or oral contraceptives.
* A tyrosine kinase inhibitor (TKI) approved by the local regulatory authority for the treatment of cancer must have been discontinued for ≥ 7 days prior to the first ALPS12 infusion; a baseline scan must be performed after discontinuation of the previous TKI, and the patient must meet the relevant criteria for adverse events (AEs) resulting from previous cancer treatment.
• Treatment with traditional Chinese medicine with anticancer activity for ≥ 7 days prior to the first ALPS12 infusion.
• Limited range of palliative radiation therapy is permitted, but must be completed before the first ALPS12 infusion.
• Prior immune checkpoint inhibitors (such as anti-PD-L1/PD-1/anti-CTLA-4/anti-LAG-3), immunomodulatory mAbs, and/or mAb-derived therapies are permitted, but the last dose of the prior therapy must be at least 4 weeks after the first ALPS12 infusion.
Patients with a history of immune-related Grade 4 AEs due to immune checkpoint inhibitors (excluding asymptomatic elevations in serum amylase or lipase).
Patients with a history of immune-related Grade 3 AEs due to immune checkpoint inhibitors (excluding asymptomatic elevations in serum amylase or lipase), resulting in permanent discontinuation of prior immunotherapy and/or occurring ≤ 6 months prior to COD1. Patients who have successfully received re-immunotherapy may be admitted.
Prior adverse events (AEs) not resolved to ≤ Grade 1 with anticancer therapy, excluding hair loss, vitiligo, Grade 2 clinically controlled immune-related toxicity sequelae associated with checkpoint inhibitors (e.g., adrenal insufficiency or hypothyroidism), Grade 2 hematologic toxicity, and Grade 2 peripheral neuropathy.
• Patients with AEs treated with corticosteroids must demonstrate ≥ 4 weeks of symptom- or symptom-free status after discontinuation of corticosteroids.
A medical history or clinical evidence of primary central nervous system (CNS) malignancy, symptomatic CNS metastases, CNS metastases requiring antitumor therapy, or leptomeningeal disease.
• Patients with previously treated CNS metastases are eligible for the trial if they meet all of the following criteria:
▪ Do not require continuous corticosteroid treatment for CNS metastases (physiological doses of steroids are permissible), and corticosteroids were discontinued ≥ 1 week prior to COD1.
▪ No persistent CNS metastatic symptoms, or the trial administrator deems the symptoms irreversible.
▪ Discontinued anticonvulsants for malignant CNS disease or using a stable dose ≥ 1 week prior to the first ALPS12 infusion.
▪ Radiation therapy was completed prior to the brain MRI scan at screening.
▪ No CNS worsening on X-ray at trial screening following definitive radiation therapy. Patients with worsening lesions after previous stereotactic radiosurgery may be eligible if the worsening is confirmed as pseudo-worsening in an appropriate manner.
▪ The patient has measurable lesions outside the CNS.
Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
Patients with a history of stroke may be admitted if they have not experienced a stroke or transient ischemic attack within the past 2 years and, in the trial administrator's opinion, have no residual neurological deficits.
Patients with a history of epilepsy may be admitted if they have not had seizures in the past 2 years and have not received any antiepileptic medication.
Those with symptomatic cerebrovascular disease (such as subarachnoid hemorrhage, cerebral infarction, or transient ischemic attack), or who had such conditions within 6 months prior to COD1.
Those with a history of pituitary inflammation or pituitary dysfunction.
Unirradiated lesions > 2 cm in diameter threatening vital organs or critical sites (such as paravertebral or paratracheal areas), which may compress critical anatomical structures due to tumor swelling (such as CNS metastases, respiratory failure due to tumor compression, or spinal cord compression), and require emergency interventional therapy.
Poorly controlled tumor-related pain.
Symptomatic lesions suitable for palliative radiotherapy (e.g., bone metastases or metastases causing nerve compression) should receive radiotherapy prior to admission.
Clinically significant pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Unilateral pleural drainage tube placement is acceptable.
Hypercalcemia (ionized calcium > 1.5 mmol/L or calcium > 12 mg/dL or corrected serum calcium ≥ ULN), or symptomatic hypercalcemia requiring continuous bisphosphonate or denosumab therapy.
• Patients receiving bisphosphonate or denosumab therapy for skeletal event prevention and without a clinically significant history of hypercalcemia are eligible.
Spinal cord compression without definitive surgical and/or radiotherapy treatment. If already treated, the patient must have achieved disease stability and have no evidence of deterioration for at least 2 weeks prior to signing the ICF.
Active or clinically significant autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-related vascular thrombosis, Wegener's granulomatosis, Schuglin syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, glomerulonephritis, pituitary inflammation, and adrenal insufficiency (such as Addison's disease), are eligible, except in the following cases:
* Patients with a history of autoimmune hypothyroidism who are receiving stable doses of thyroid hormone replacement therapy are eligible.
* Patients with well-controlled type 1 diabetes are eligible.
* Patients with eczema, psoriasis, chronic simple lichen simplex, or vitiligo who have symptoms limited to the skin (e.g., non-psoriatic arthritis) and meet the following criteria are eligible:
* The affected area must be less than 10% of the body surface area.
* The disease was effectively controlled at baseline, requiring only low-potency topical steroid therapy.
No acute exacerbations of underlying disease within the past 12 months (e.g., no need for PUVA, folate, retinoic acid, biologics, oral calcineurin inhibitors, potent or oral steroid therapy).
Use of systemic immunosuppressive drugs within 1 week prior to COD1 (including, but not limited to, more than 10 mg/day of prednisone or equivalent doses of conventional corticosteroids, cyclophosphamide, azathioprine, folate, thalidomide, tumor necrosis factor [TNF-α] antagonists), or anticipated immunosuppression during the trial, except in the following circumstances:
* Pre-treatment with steroids to prevent allergic reactions (e.g., pre-treatment before CT scans)
* Inhaled, intranasal, intra-articular, or topical corticosteroids are permissible (e.g., fluticasone for treating chronic obstructive pulmonary disease).
* Oral mineral corticosteroids are permissible (e.g., fludrocortisone for patients with postural hypotension).
Patients with a history of interstitial lung disease, drug-induced pneumonia, or evidence of active pneumonia on a chest CT scan at screening are eligible.
Patients with a history of radiation-induced pneumonia (fibrosis) in the radiation-treated area are also eligible.
Patients with known clinically significant liver disease, including alcoholic or other hepatitis, cirrhosis, hereditary liver disease, current alcohol abuse, active hepatitis B (defined as a positive hepatitis B surface antigen [HBsAg] test at screening), or active hepatitis C are eligible.
Patients with a history of hepatitis B infection or in remission (defined as a negative HBsAg test and a positive hepatitis B core [anti-HBc] antigen IgG antibody) are eligible. These patients must have a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) sample obtained before COD1. Eligible HBV DNA-negative patients will receive obinutuzumab. HBV DNA results will need to be monitored monthly for 12 months after the last dose of obinutuzumab.
• Patients with positive hepatitis C virus (HCV) antibodies must have a negative HCV RNA PCR test to be eligible.
Severe infection within 4 weeks prior to COD1, including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia.
Clinically significant recent infection, but not meeting the above severe infection criteria, including the following:
• Clinically significant signs or symptoms of infection within 2 weeks prior to COD1.
• Received oral or intravenous antibiotics within 2 weeks prior to COD1.
▪ Patients receiving prophylactic antibiotic treatment (e.g., for prophylaxis of urinary tract infections or chronic obstructive pulmonary disease) are eligible.
Patients must have received a live attenuated vaccine within 4 weeks prior to COD1, or are expected to receive a live attenuated vaccine during the trial, within 40 days of the last dose of ALPS12, or within 18 months of the last dose of obinutuzumab (whichever is longer).
• COVID-19 vaccines may be administered during the trial, but must be locally approved and non-live vaccines. Vaccination during DLT should be avoided whenever clinically appropriate.
Patients with a history of progressive multifocal leukoencephalopathy (MLLE).
Poorly controlled type 2 diabetes, defined as HbA1c ≥ 8% or fasting blood glucose ≥ 160 mg/dL (or 8.8 mmol/L) at screening.
Clinically significant major surgery or traumatic injury within 28 days prior to COD1 (as determined by the trial administrator), or anticipated major surgery during the trial.
Patients with a history of malignant tumors but with an extremely low risk of metastasis or death (e.g., appropriately treated cervical carcinoma in situ, basal cell carcinoma of the skin, localized prostate cancer, ductal carcinoma in situ of the breast, or cured resection of thyroid cancer with good histological condition) are eligible for inclusion.
Patients with malignant tumors who have received radical treatment and have been in tumor remission for ≥ 2 years prior to the first ALPS12 infusion without further treatment are also eligible for inclusion.
Patients must have received other investigational treatment within 21 days prior to starting C0D1.
QT interval (QTcF) corrected according to the Fridericia formula > 470 ms. Abnormal electrocardiogram findings (repeated three times, with intervals > 30 minutes).
A history of ventricular arrhythmias or risk factors for ventricular arrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary artery disease (with symptoms or confirmed by diagnostic tests as focal ischemia), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or a family history of unexplained sudden death or QT prolongation syndrome.
Current drug treatment is known to prolong the QT interval.
Previous treatment with anti-CD137 drugs, anti-CD3 drugs, and/or DLL3 targeted therapy.
The patient must have received anticancer therapy, whether investigational or approved, including chemotherapy, hormone therapy, and/or radiation therapy, within 21 days prior to the initiation of the first ALPS12 infusion, except in the following cases:
* Prior cancer vaccine and/or cytokine therapy, provided that at least 4 weeks or 5 drug half-lives (whichever is shorter) separate the last dose of the prior therapy from the first ALPS12 infusion.
* Received prostate cancer GnRH agonist or antagonist hormone therapy.
* Hormone replacement therapy or oral contraceptives.
* A tyrosine kinase inhibitor (TKI) approved by the local regulatory authority for the treatment of cancer must have been discontinued for ≥ 7 days prior to the first ALPS12 infusion; a baseline scan must be performed after discontinuation of the previous TKI, and the patient must meet the relevant criteria for adverse events (AEs) resulting from previous cancer treatment.
• Treatment with traditional Chinese medicine with anticancer activity for ≥ 7 days prior to the first ALPS12 infusion.
• Limited range of palliative radiation therapy is permitted, but must be completed before the first ALPS12 infusion.
• Prior immune checkpoint inhibitors (such as anti-PD-L1/PD-1/anti-CTLA-4/anti-LAG-3), immunomodulatory mAbs, and/or mAb-derived therapies are permitted, but the last dose of the prior therapy must be at least 4 weeks after the first ALPS12 infusion.
Patients with a history of immune-related Grade 4 AEs due to immune checkpoint inhibitors (excluding asymptomatic elevations in serum amylase or lipase).
Patients with a history of immune-related Grade 3 AEs due to immune checkpoint inhibitors (excluding asymptomatic elevations in serum amylase or lipase), resulting in permanent discontinuation of prior immunotherapy and/or occurring ≤ 6 months prior to COD1. Patients who have successfully received re-immunotherapy may be admitted.
Prior adverse events (AEs) not resolved to ≤ Grade 1 with anticancer therapy, excluding hair loss, vitiligo, Grade 2 clinically controlled immune-related toxicity sequelae associated with checkpoint inhibitors (e.g., adrenal insufficiency or hypothyroidism), Grade 2 hematologic toxicity, and Grade 2 peripheral neuropathy.
• Patients with AEs treated with corticosteroids must demonstrate ≥ 4 weeks of symptom- or symptom-free status after discontinuation of corticosteroids.
A medical history or clinical evidence of primary central nervous system (CNS) malignancy, symptomatic CNS metastases, CNS metastases requiring antitumor therapy, or leptomeningeal disease.
• Patients with previously treated CNS metastases are eligible for the trial if they meet all of the following criteria:
▪ Do not require continuous corticosteroid treatment for CNS metastases (physiological doses of steroids are permissible), and corticosteroids were discontinued ≥ 1 week prior to COD1.
▪ No persistent CNS metastatic symptoms, or the trial administrator deems the symptoms irreversible.
▪ Discontinued anticonvulsants for malignant CNS disease or using a stable dose ≥ 1 week prior to the first ALPS12 infusion.
▪ Radiation therapy was completed prior to the brain MRI scan at screening.
▪ No CNS worsening on X-ray at trial screening following definitive radiation therapy. Patients with worsening lesions after previous stereotactic radiosurgery may be eligible if the worsening is confirmed as pseudo-worsening in an appropriate manner.
▪ The patient has measurable lesions outside the CNS.
Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
Patients with a history of stroke may be admitted if they have not experienced a stroke or transient ischemic attack within the past 2 years and, in the trial administrator's opinion, have no residual neurological deficits.
Patients with a history of epilepsy may be admitted if they have not had seizures in the past 2 years and have not received any antiepileptic medication.
Those with symptomatic cerebrovascular disease (such as subarachnoid hemorrhage, cerebral infarction, or transient ischemic attack), or who had such conditions within 6 months prior to COD1.
Those with a history of pituitary inflammation or pituitary dysfunction.
Unirradiated lesions > 2 cm in diameter threatening vital organs or critical sites (such as paravertebral or paratracheal areas), which may compress critical anatomical structures due to tumor swelling (such as CNS metastases, respiratory failure due to tumor compression, or spinal cord compression), and require emergency interventional therapy.
Poorly controlled tumor-related pain.
Symptomatic lesions suitable for palliative radiotherapy (e.g., bone metastases or metastases causing nerve compression) should receive radiotherapy prior to admission.
Clinically significant pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Unilateral pleural drainage tube placement is acceptable.
Hypercalcemia (ionized calcium > 1.5 mmol/L or calcium > 12 mg/dL or corrected serum calcium ≥ ULN), or symptomatic hypercalcemia requiring continuous bisphosphonate or denosumab therapy.
• Patients receiving bisphosphonate or denosumab therapy for skeletal event prevention and without a clinically significant history of hypercalcemia are eligible.
Spinal cord compression without definitive surgical and/or radiotherapy treatment. If already treated, the patient must have achieved disease stability and have no evidence of deterioration for at least 2 weeks prior to signing the ICF.
Active or clinically significant autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-related vascular thrombosis, Wegener's granulomatosis, Schuglin syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, glomerulonephritis, pituitary inflammation, and adrenal insufficiency (such as Addison's disease), are eligible, except in the following cases:
* Patients with a history of autoimmune hypothyroidism who are receiving stable doses of thyroid hormone replacement therapy are eligible.
* Patients with well-controlled type 1 diabetes are eligible.
* Patients with eczema, psoriasis, chronic simple lichen simplex, or vitiligo who have symptoms limited to the skin (e.g., non-psoriatic arthritis) and meet the following criteria are eligible:
* The affected area must be less than 10% of the body surface area.
* The disease was effectively controlled at baseline, requiring only low-potency topical steroid therapy.
No acute exacerbations of underlying disease within the past 12 months (e.g., no need for PUVA, folate, retinoic acid, biologics, oral calcineurin inhibitors, potent or oral steroid therapy).
Use of systemic immunosuppressive drugs within 1 week prior to COD1 (including, but not limited to, more than 10 mg/day of prednisone or equivalent doses of conventional corticosteroids, cyclophosphamide, azathioprine, folate, thalidomide, tumor necrosis factor [TNF-α] antagonists), or anticipated immunosuppression during the trial, except in the following circumstances:
* Pre-treatment with steroids to prevent allergic reactions (e.g., pre-treatment before CT scans)
* Inhaled, intranasal, intra-articular, or topical corticosteroids are permissible (e.g., fluticasone for treating chronic obstructive pulmonary disease).
* Oral mineral corticosteroids are permissible (e.g., fludrocortisone for patients with postural hypotension).
Patients with a history of interstitial lung disease, drug-induced pneumonia, or evidence of active pneumonia on a chest CT scan at screening are eligible.
Patients with a history of radiation-induced pneumonia (fibrosis) in the radiation-treated area are also eligible.
Patients with known clinically significant liver disease, including alcoholic or other hepatitis, cirrhosis, hereditary liver disease, current alcohol abuse, active hepatitis B (defined as a positive hepatitis B surface antigen [HBsAg] test at screening), or active hepatitis C are eligible.
Patients with a history of hepatitis B infection or in remission (defined as a negative HBsAg test and a positive hepatitis B core [anti-HBc] antigen IgG antibody) are eligible. These patients must have a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) sample obtained before COD1. Eligible HBV DNA-negative patients will receive obinutuzumab. HBV DNA results will need to be monitored monthly for 12 months after the last dose of obinutuzumab.
• Patients with positive hepatitis C virus (HCV) antibodies must have a negative HCV RNA PCR test to be eligible.
Severe infection within 4 weeks prior to COD1, including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia.
Clinically significant recent infection, but not meeting the above severe infection criteria, including the following:
• Clinically significant signs or symptoms of infection within 2 weeks prior to COD1.
• Received oral or intravenous antibiotics within 2 weeks prior to COD1.
▪ Patients receiving prophylactic antibiotic treatment (e.g., for prophylaxis of urinary tract infections or chronic obstructive pulmonary disease) are eligible.
Patients must have received a live attenuated vaccine within 4 weeks prior to COD1, or are expected to receive a live attenuated vaccine during the trial, within 40 days of the last dose of ALPS12, or within 18 months of the last dose of obinutuzumab (whichever is longer).
• COVID-19 vaccines may be administered during the trial, but must be locally approved and non-live vaccines. Vaccination during DLT should be avoided whenever clinically appropriate.
Patients with a history of progressive multifocal leukoencephalopathy (MLLE).
The Estimated Number of Participants
-
Taiwan
14 participants
-
Global
122 participants
