Evaluate the Safety and Tolerability of JCXH-212 Monotherapy and Combined With Toripalimab in the Treatment of Malignant Solid Tumors

NCT05579275 | Recruiting Early Phase 1

• 1 other identifier: 2021-JCXH-212-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of JCXH-212 monotherapy and combined with Toripalimab in patients with malignant solid tumors; to determine the maximum tolerated dose (MTD), and to evaluate the dose-limiting toxicity (DLT) of JCXH-212 monotherapy and combined with Toripalimab.

Conditions

Malignant Solid Tumors

Outcome Measures

Primary Outcomes (2)

• dose-limiting toxicity (DLT)

  Tolerability and safety analysis: determine the maximum tolerated dose (MTD) and determine the escalation of the relevant dose. Incidence of DLTs was summarized overall and by dose level based on the DLT Analysis Set (DLTS).

  Up to 21 days after first dose every subject

• analysis of primary efficacy indicators

  Efficacy analysis: In the study, correlation analysis will be performed between the main efficacy indicators and dose regimen in each dose group.

  At the end of the time 3-6 months after last subject last dose

Secondary Outcomes (1)

• exploratory analysis of changes in peripheral blood neoantigen-specific T cell responses before and after administration

  The day of administration of the last subject

Study Arms (1)

cohort-experimental

EXPERIMENTAL

Patients will receive treatment for up to 1 year. Actual follow-up will be decided according to the patient 's condition and benefit, and each test requirement and data collection will be completed at specified time during the follow-up cycle.

Biological: JCXH-212 Injection

Interventions

JCXH-212 Injection BIOLOGICAL

Based on the development principle of NCV, a community-type tumor neoantigen mRNA vaccine, JCXH-212 injection, has been developed that can be applied to patients with malignant solid tumors. NCVs activate tumor-specific CD4+ T cells and CD8+ T cells through active immunity, and these T cells can inhibit and kill tumor cells in cancer patients, thus prolonging the survival of cancer patients.

cohort-experimental

Eligibility Criteria

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

You may qualify if:

• The enrolled subjects shall meet all the following conditions at the same time:
• male or female patients, aged 18 \~ 75 years old;
• patients with advanced malignant solid tumors who have failed standard treatment (progression or intolerance after treatment) confirmed by pathology and/or cytology (only for Part 1);
• only for part2 : A. Patients with initial treatment, refusing or intolerant of standard treatment, PD-L1 (IHC 22C3) TPS ≥ 1%; B. Stage IIIB-IV patients with disease progression after previous standard treatment, who intend to receive immune monotherapy, can be enrolled regardless of the results of PD-L1; C. Stage II-III NSCLC patients after radical surgery, postoperative adjuvant chemotherapy (if necessary) has been completed, and PD-L1 (IHC 22c3) TPS is ≥ 1%, intend to receive adjuvant immunotherapy.
• tumor biopsy tissue samples can be provided for tumor neoantigen detection;
• ECOG (Eastern Cooperative Oncology Group) score of 0 \~ 1 in general condition;
• expected survival time of more than 3 months;
• patients have at least one measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECISTv1.1), the longest diameter at baseline is ≥ 10 mm (if lymph nodes, the short diameter is ≥ 15 mm);
• patients shall have sufficient bone marrow reserve function, and have no liver and kidney coagulation dysfunction, and laboratory test values shall meet the following conditions:
• absolute neutrophil count \> 1.5 × 10/L, And white blood cell count \> 3 × 10/L;
• platelet count \> 80 × 10/L;
• hemoglobin \> 90 g/L;
• serum creatinine \< 1.5 × upper limit of normal (ULN) and creatinine clearance calculated by Cockroft-Gault formula \> 30 mL/min;
• if there is no confirmed liver metastasis, AST, ALT \< 2.5 × ULN; if there is confirmed liver metastasis, AST, ALT \< 5 × ULN;
• if there is no liver metastasis, total bilirubin \< 1.5 × ULN; if there is liver metastasis or Gilbert 's syndrome (hyperindirect bilirubinemia), total bilirubin \< 3 × ULN;

You may not qualify if:

• Those meeting any of the following conditions may not be included.
• Known or suspected hypersensitivity to the ingredients of the study drug or its analogues;
• Only for Part 2: adverse reactions of grade ≥3 occurred after using ICIs in the past; except maculopapules /itching and reactive cutaneous capillary hyperplasia (RCCEP), there is no need to stop ICIs in hypothyroidism. Or those who are at high risk of receiving ICI treatment.
• Patients with any other disease or medical condition that is unstable or may affect their safety or study compliance, any serious or uncontrolled systemic disease, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, active gastrointestinal ulcers, abnormal immune function, etc.;
• Cardiovascular and cerebrovascular diseases/symptoms/indications that meet any of the following conditions:
• mean resting QTc \> 470 ms (corrected QT interval \[corrected by Fridericia formula\]), mean QTc of 3 ECGs, QT interval measurement should start from QRS complex to the end of T wave);
• any clinically significant resting ECG abnormalities in rhythm, conduction or morphology, such as complete left bundle branch block, grade 2 and 3 heart block, PR interval \> 250 ms, etc.;
• any factor that increases the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, etc. or unexplained sudden death in a first-degree relative under 40 years of age, or any concomitant medication known to prolong the QT interval;
• left ventricular ejection fraction (LVEF) \< 50%;
• previous history of decreased myocardial contractility, i.e.Patients who presented with relevant symptoms within 6 months before study drug administration: such as chronic congestive heart failure, pulmonary edema or decreased cardiac ejection fraction;
• patients who had a history of acute or chronic cardiovascular and cerebrovascular diseases and presented with relevant symptoms within 6 months before study drug administration: myocardial infarction, severe or unstable angina pectoris, cerebral infarction, cerebral hemorrhage, or transient ischemic attack;
• Patients who had an active second primary malignant tumor within 2 years before the first dose of study drug, except for specific cancers to be investigated and locally recurrent cancers that had undergone radical treatment (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ);
• Patients with uncontrollable malignant third space effusion;
• For women of childbearing age (postmenopausal women must have been postmenopausal for at least 12 months to be considered of non-childbearing potential), positive serum pregnancy test results within 7 days before the first dose of study drug;
• Have received major surgery within 4 weeks before the first administration of the study drug; Before receiving the study drug for the first time, the elution period for previous anti-cancer treatments (chemotherapy, targeted drugs, immunotherapy and radiotherapy) or any other study treatment is less than 3 weeks or 5 half-lives, whichever is shorter.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, 100042, China

RECRUITING

Study Officials

• Zhuo Minglei, Physician

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

• zhuo Minglei, Physician

  Peking University Cancer Hospital & Institute

  STUDY CHAIR

Central Study Contacts

Zhuo Minglei, Physician

CONTACT

010-88196456; trialminglei@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: September 30, 2022
• First Posted: October 13, 2022
• Study Start: February 6, 2023
• Primary Completion: April 28, 2026
• Study Completion (Estimated): April 28, 2027
• Last Updated: May 14, 2024

Record last verified: 2024-05

Locations

CN (1)