Phase 2 Cachexia Clinical Trial to Evaluate the Efficacy and Safety of ASCA101

Inclusion criteria

To be eligible for enrollment, subjects must meet all of the following criteria.

• Aged 19 years or older with a histologically or cytologically confirmed diagnosis of a solid tumor (primary tumor types: colorectal cancer, ovarian cancer, and lung cancer [lung cancer applicable to Study 1 only]).
• Must be either surgically sterilized or postmenopausal*. (For female subjects only)

*Postmenopause is defined as the permanent cessation of ovarian function, evidenced by the absence of menstruation for 12 consecutive months not attributable to other medical causes.

• Must meet at least one of the following criteria consistent with cachexia diagnosis*:

① Unintentional weight loss of >5% over the past 6 months.

② BMI <20 kg/m² with unintentional weight loss of >2% over the past 6 months.

③ Diagnosis of sarcopenia (skeletal muscle index: <7.26 kg/m² for men, <5.45 kg/m² for women) with unintentional weight loss of >2% over the past 6 months.

*For subjects requiring confirmation of sarcopenia for cachexia diagnosis, skeletal muscle mass must be assessed using Dual-Energy X-ray Absorptiometry (DEXA).

• Clinical laboratory results measured within 14 days prior to randomization must meet the following criteria :

• Absolute Neutrophil Count (ANC) ≥ 1,000/mm³

• Platelet count ≥ 75,000/mm³

• Hemoglobin ≥ 8.0 g/dL ④ Serum creatinine ≤ 2 × upper limit of normal (ULN) ⑤ Total bilirubin ≤ 3 × ULN ⑥ AST and ALT ≤ 3 × ULN (≤ 5 × ULN if liver metastasis is present)

• INR and aPTT ≤ 1.5 × ULN
• Able to consume food orally.
• Able to complete questionnaires.
• Life expectancy of at least 16 weeks, as assessed by the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3.
• Male subjects who have not undergone vasectomy must agree to use highly effective contraception from at least 4 weeks prior to study drug administration, throughout the study period, and for 6 months following the last dose.

Highly effective contraception includes: partner's hormonal contraception, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, or total sexual abstinence.

• Able and willing to voluntarily provide written informed consent to participate in this clinical trial.

Exclusion criteria

Subjects meeting any of the following criteria will be excluded from enrollment.

• Patients who meet any of the following criteria:

① Are scheduled to undergo surgery requiring general anesthesia for the treatment of cancer.

② Are scheduled to switch to, or initiate an additional anticancer treatment regimen other than the chemotherapy (including chemoimmunotherapy) or radiotherapy currently being administered.

③ Are receiving, or are scheduled to receive, hormonal therapy or immunotherapy.

• History of hypersensitivity to any component of the investigational product or to drugs of the same class.
• Currently taking medications for the purpose of appetite stimulation or weight gain.
• History of surgery within 3 months prior to screening. (Note: Subjects undergoing postoperative chemotherapy are eligible regardless of the time of surgery.)
• Subjects requiring dietary restrictions.
• Subjects requiring enteral or parenteral nutrition.
• Weight loss due to causes other than malignancy, including:

• Major endocrine/metabolic disorders (e.g., hyperthyroidism, uncontrolled diabetes mellitus)
• Conditions affecting appetite or calorie intake (e.g., mechanical bowel obstruction, cholestasis, uncontrolled nausea/vomiting, malabsorption syndromes, severe diarrhea)
• Conditions that may lead to weight gain, including major endocrine/metabolic diseases (e.g., hypothyroidism, Cushing's syndrome).
• History of any of the following cardiovascular conditions within the past 5 years:

• Congestive heart failure (CHF) classified as NYHA Class II or higher, or LVEF

• 50%
• Uncontrolled hypertension
• History of hypertensive crisis or hypertensive encephalopathy
• Pulmonary hypertension
• Myocardial infarction
• Clinically significant vascular disease within 6 months prior to the first dose (e.g., aneurysm requiring surgery, recent peripheral arterial thrombosis)
• Uncontrolled arrhythmias
• Persistent clinically significant toxicity (Grade ≥2 per NCI-CTCAE v5.0) due to previous cancer treatment.
• Subjects with severe infections or severe traumatic systemic conditions.
• Symptomatic or uncontrolled central nervous system (CNS) metastases. (Note: Subjects with asymptomatic CNS metastases who have discontinued systemic corticosteroids at least 4 weeks prior to randomization and have been radiologically and neurologically stable for ≥4 weeks are eligible.)
• Patients with one or more contraindications to ascorbic acid injection and/or calcium injection, including:

• Hyperoxaluria, thalassemia
• Gout, cystinuria
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Calcium oxalate nephrolithiasis
• Receiving cardiac glycosides
• Hypercalcemia (Ca ≥10.5 mg/dL)
• History of kidney stones with hypercalciuria
• Sarcoidosis
• Nephrolithiasis
• Hypoproteinemia (Total protein ≤6.0 g/dL)
• Severe renal impairment (eGFR < 30 mL/min)
• Patients with severe neurological or psychiatric disorders that, in the investigator's judgment, are sufficient to affect the clinical trial outcomes (e.g., depression, dementia, delirium).
• Patients who are breastfeeding or who, or whose partners, are planning to become pregnant during the clinical trial period.
• Individuals who have participated in another clinical trial within 30 days prior to screening.
• Patients with a history of bleeding-related or gastrointestinal diseases, as described below:

• Evidence of active bleeding, bleeding diathesis, coagulopathy, or tumors involving major blood vessels.
• Clinically significant peptic ulcers, gastrointestinal bleeding, gastrointestinal or non-gastrointestinal fistulas, perforations, intra-abdominal abscesses, signs or symptoms of gastrointestinal obstruction, requirement of parenteral hydration or nutrition, or a history of inflammatory bowel disease (IBD).
• Evidence of free air in the abdomen not explained by paracentesis or recent surgical procedures.
• Patients who have received biguanides (e.g., metformin) within 2 weeks prior to screening or are expected to require them during the clinical trial.
• Patients requiring continuous systemic corticosteroid therapy (exceptions allowed as below):

• Use of local corticosteroids such as intra-articular, intranasal, ophthalmic, or inhaled corticosteroids is permitted.
• Temporary systemic corticosteroid use for treatment or prevention of contrast agent allergy or adverse events is allowed.
• Patients with HIV or other severe diseases deemed by the investigator to make study participation inappropriate.
• Patients who underwent drainage of ascites and/or pleural effusion within 14 days prior to screening.
• Patients with hemoptysis (defined as ≥1/2 teaspoon of bright red blood per episode) within 14 days prior to screening.
• Patients who underwent core biopsy or other minor surgical procedures (excluding vascular access device placement) within 3 days prior to the first administration of the investigational product.
• Patients with significant, unhealed wounds, active ulcers, or untreated fractures.
• Patients with a history of cerebrovascular accident (stroke), transient ischemic attack, or subarachnoid hemorrhage within 6 months prior to screening.
• Patients with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Any other condition deemed by the investigator to make the patient unsuitable for participation in the clinical trial.

[Exclusion Criteria Applicable Only to Study 1]

• Patients with a history of hypersensitivity to megestrol acetate or any of its components.
• Patients who have been receiving continuous antithrombotic therapy (antiplatelet agents, oral anticoagulants, or a combination thereof) within 4 weeks prior to screening, or who are anticipated to require antithrombotic therapy during the study period.
• Patients with diabetes mellitus.