Safety and Toxicity Study of IMM27M in Patients With Advanced Solid Tumor

NCT05235438 | Unknown Phase 1

• 1 other identifier: IMM27M-001
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

Brief Summary

This is a single arm, open label, multi-center and fist in human dose escalation study, to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with advanced and metastatic solid tumor.

Conditions

Oncology; CTLA4 Haploinsufficiency

Outcome Measures

Primary Outcomes (3)

• a dose-limiting toxicity (DLT)

  the DLT of IMM27M

  3 weeks

• The maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)

  3 weeks

• the rate of adverse events

  the rate of adverse event (AE), severity and relationship of IMM27M based on CTCAE 5.0

  48 weeks

Secondary Outcomes (13)

• Maximum Plasma Concentration (Cmax)

  48 weeks

• Dose escalation: Overall Response Rate (ORR)

  48 weeks

• Dose escalation : Clinical Benefit Rate (CBR)

  48 weeks

• Dose escalation : Duration of Response (DOR)

  48 weeks

• Dose escalation: Progression-Free Survival (PFS)

  48 weeks

Study Arms (1)

IMM27M

EXPERIMENTAL

IMM27M 0.1, 0.3, 1.0, 2.0, 3.0 mg/kg

Drug: IMM27M

Interventions

IMM27M DRUG

IMM27M injection

IMM27M

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign an Informed Consent Form voluntarily and comply with the protocol requirements;
• Age ≥18 years old, and ≤75 years old, regardless of gender;
• Expected survival ≥12 weeks;
• Clinical diagnosis:
• Phase Ia: Patients with advanced or recurrent solid tumors diagnosed by histology or cytology, who have previously received standard treatment progress or treatment failure (including progress or relapse after PD-1/PD-L1 inhibitor treatment). Or there is no standard treatment regimen at this stage, including but not limited to malignant melanoma, hepatocellular carcinoma, non-small cell lung cancer, colorectal cancer, ovarian cancer, endometrial cancer, triple negative breast cancer, small cell lung cancer, renal cell carcinoma, squamous cell cancer of head and neck, pancreatic cancer, etc.;
• Archived tumor histology and pathology reports from fresh or recent treatment can be provided. If tissue specimens are not available, re-biopsy of the tumor is recommended for patients.
• Lesions can be measured according to the evaluation criteria for solid tumors (RECIST v1.1) (the longest diameter of the spiral CT scan ≥ 10 mm, if the lesion is a lymph node, the short diameter ≥ 15 mm; and radiotherapy has not be performed on the lesion);
• The performance status ECOG is 0 or 1;
• For hepatocellular carcinoma (HCC) patients, a Child-Pugh score of A is required, without ascites or hepatic encephalopathy;
• The organ function level should meet the following requirements:
• Bone marrow: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥85×109/L, hemoglobin ≥90 g/L, and have not received blood transfusion or biological response modifiers (such as granulocyte growth promoting factor, red blood cell growth factor, etc.) ; Note: HCC patients with liver cirrhosis with ANC ≥1.0×109/L and platelet count ≥70×109/L are eligible for enrollment.
• Liver: total bilirubin (TBIL)≤1.5×ULN, alkaline phosphatase (ALP)≤1.5×ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN; if there is liver metastasis, then TBIL≤3.0×ULN, AST and ALT are ≤5.0×ULN; Note: HCC patients with liver cirrhosis with AST and ALT≤5×ULN, TBIL≤3.0×ULN, and albumin ≥2.8g/L are eligible for enrollment.
• Heart: Left ventricular ejection fraction (LVEF) ≥50% (ECHO confirmed);
• Kidney: Creatinine (Cr)≤1.5×ULN, or creatinine clearance (Ccr)≥50 mL/min (according to Cockcroft-Gault formula).
• Thyroid: Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, the levels of FT3 and FT4 should be observed at the same time, if the levels of FT3 and FT4 are normal, they can enroll);

You may not qualify if:

• Treatment with the last systemic anti-tumor therapy within 4 weeks prior to the first administration, including chemotherapy, immunotherapy, biotherapy and so on; treatment with hormone anti-tumor therapy and small-molecule targeted therapy within 2 weeks prior to the first administration; palliative local treatment for non-target lesions within 2 weeks prior to the first administration; treatment with non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 for the treatment of thrombocytopenia) within 2 weeks prior to the first administration; treatment with Chinese herbal medicine or Chinese patent medicine with anti-tumor indications within 1 week prior to the first administration.
• Treatment with anti-CTLA-4 inhibitors and anti-PD-1/L1 inhibitors 4 weeks before the first administration;
• Patients with primary central nervous system (CNS) malignant tumors or patients with active metastasis of CNS after local treatment failure (radiotherapy or surgery), but the following patients are allowed to be enrolled: a. Asymptomatic brain metastases; b. Clinical symptoms are stable (i.e., no radiographic progression and all neurological symptoms have returned to baseline 4 weeks before the first administration), and no corticosteroid treatment and other treatments for brain metastasis are required ≥ 4 weeks;
• Hypertension (systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg), pulmonary hypertension or unstable angina, which cannot be controlled by medication; treatment with myocardial infarction, bypass or stent surgery within 6 months prior to administration; a history of chronic heart failure rated by the New York Heart Association (NYHA) as grade 3-4; valvular disease with clinical significance; severe arrhythmia requiring treatment (excluding atrial fibrillation and paroxysmal supraventricular tachycardia), including QTcF≥450ms for male and ≥470ms for female (calculated by Fridericia formula); cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 12 months prior to enrollment;
• A history of arterial thrombosis, deep venous thrombosis and pulmonary embolism within 3 months prior to administration;
• A history of moderate or severe dyspnea at rest due to an advanced malignant tumor or its complications or severe primary pulmonary disease, or a current need for continuous oxygen therapy, or a current history of interstitial lung disease (ILD) or pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.;
• Development of other malignant tumors within 5 years prior to the first administration. Exceptions: a. Radically cured cervical carcinoma in situ or non-melanoma skin cancer; b. A second primary carcinoma that has been radically cured and has not recurred within 5 years; c. All double primary carcinoma patients can benefit from this study in the opinion of investigators; d. Investigators have definitively excluded what kind of primary tumor the metastasis belongs to;
• Diseases that may cause gastrointestinal bleeding or perforation (such as duodenal ulcer, intestinal obstruction, acute Crohn's disease, ulcerative colitis, large area gastric and small bowel resection, etc.); patients with chronic Crohn's disease and ulcerative colitis (except for total colon and rectal resection) should be excluded even in inactive phase; patients with hereditary non-polyposis colorectal cancer or familial adenomatous polyposis syndrome; patients with a history of intestinal perforation and intestinal fistula who have not been recovered after surgical treatment; patients with esophageal and gastric varices;
• Puncture and drainage is needed to treat uncontrollable pleural-peritoneal and pericardial effusions that need repeated drainage or with obvious symptoms;
• Those with active hepatitis B (HBsAg positive, HBV DNA ≥2000 IU/ml, and excluding hepatitis caused by drugs or other reasons), or active hepatitis C (anti-HCV antibody positive, and HCV RNA higher than lower detection limit);
• Patients with a history of immunodeficiency, including human immunodeficiency virus (HIV) infection, or other immunodeficiency diseases, or a history of organ transplants;
• Patients with a history of autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, autoimmune thyroid disease, multiple sclerosis, etc. patient. A history of auto-immune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, autoimmune thyroid disorder, multiple sclerosis, etc. Exceptions:
• Hypothyroidism that can be controlled by hormone replacement therapy alone;
• Dermatosis that does not require systemic therapies (such as vitiligo, psoriasis);
• Controlled coeliac disease. Currently under treatment with immunosuppressive agents or systemic hormone therapy (≥10mg/day of prednisone or other hormone equivalents), and still under continued use within 2 weeks prior to enrollment;

Sponsors & Collaborators

• ImmuneOnco Biopharmaceuticals (Shanghai) Inc.: lead

Study Sites (6)

Peking University First Hospital

Beijing, China

RECRUITING

Sun Yai-Sen Memorial Hospital,Sun Yai-Sen University

Guangzhou, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, China

RECRUITING

Henan Cancer Hospital

Henan, China

RECRUITING

The First Affiliated Hospital of Xi'An Jiaotong University

Xi'an, China

RECRUITING

MeSH Terms

Conditions

Neoplasms; Diabetes Mellitus, Insulin-Dependent, 12

Central Study Contacts

jinhua zhou

CONTACT

02138016387; jinhua.zhou@immuneonco.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is to observe the dose-limiting toxicity (DLT) of the patients and to determine the maximal tolerance dose(MTD) and recommended dose for expansion (RDE) to observe the AE including relationship and severity of IMM27M based on CTCAE 5.0

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: February 11, 2022
• Study Start: June 15, 2022
• Primary Completion: August 30, 2023
• Study Completion: August 30, 2024
• Last Updated: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)