Clinical Study of CVL006 Injection in Advanced Solid Tumors

NCT06621615 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CVL006-T1001
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

Evaluate the safety and tolerability of CVL006 monotherapy in patients with advanced solid tumors; Observe the dose limiting toxicity (DLT) of CVL006 monotherapy in patients with advanced solid tumors, evaluate the maximum tolerated dose (MTD), and recommend the dosage for phase II clinical trials (RP2D).

Conditions

Advanced Solid Tumor

Keywords

Late stage solid tumor; DLT; MTD; RP2D

Outcome Measures

Primary Outcomes (3)

• DLT of CVL006 monotherapy in advanced solid tumor patients.

  Safety events that occur during the DLT observation period and are determined by researchers to be related to the investigational drug.

  In Phase Ia trials, if there is a delay in the second administration 28 days after the first dose, the DLT observation period will be extended to 14 days after the second administration.

• MTD of CVL006 monotherapy in patients with advanced solid tumors.

  During the DLT observation period, the highest dose at which ≤ 1 subject experienced DLT and could not continue to increase in dose among at least 6 subjects

  Phase Ia trial, from the first subject to the end of the DLT observation period for the last subject.

• RP2D of CVL006 monotherapy in patients with advanced solid tumors

  RP2D is an extended study conducted through dose escalation stage exploration, recommended by SMC, to obtain sufficient safety, tolerability, PK, and preliminary efficacy results. The dosage selected for subsequent efficacy expansion stage is further discussed and confirmed by SMC. RP2D should not exceed the MTD obtained by dose escalation.

  From the first subject enrolled in Phase 1a to the last subject removed from Phase Ib.

Secondary Outcomes (3)

• Objective response rate (ORR) in patients

  Throughout the study for approximately 5 years.

• Progression-free survival (PFS)

  Throughout the study for approximately 5 years.

• Overall Survival (OS)

  Throughout the study for approximately 5 years.

Study Arms (1)

CVL006 monotherapy group

EXPERIMENTAL

This study is divided into three stages. Ia. Dose escalation stage: Accelerated titration combined with a "3+3" design was used for dose escalation, with a maximum enrollment of 42 subjects. Ib. Dose extension stage: Based on the data from dose escalation, in dose groups where a certain therapeutic effect is observed, each dose group will be extended by no more than 10 subjects, and RP2D will be determined based on the data from dose escalation and extension stages. Ic. Efficacy expansion stage: RP2D was selected for expansion, with each tumor type expanded to 10-30 cases. The above three stages involve intravenous infusion of CVL006, administered every 2 weeks and every 28 days as a treatment cycle. The first treatment cycle (28 days) serves as the DLT observation period, during which DLT is collected and its MTD and RP2D are determined.

Biological: CVL006 Injection

Interventions

CVL006 Injection BIOLOGICAL

CVL006 injection, intravenous infusion, administered every 2 weeks. Every 28 days is a cycle. Until the subject cannot tolerate the disease progression or toxicity, or the researcher determines that the medication must be terminated or the sponsor terminates the study. SMC can adjust the dosing frequency based on safety, tolerability, and PK results data. If researchers consider that subjects enrolled in the lower dose group can benefit from the study intervention, they can allow them to continue treatment at a higher dose that has been proven safe based on the researcher's judgment.

Also known as: B006

CVL006 monotherapy group

Eligibility Criteria

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

You may qualify if:

• Age: 18\~75 years old (including both ends), gender not limited;
• Dose escalation and dose expansion stage: For patients with advanced malignant solid tumors confirmed by histology or cytology, if standard treatment has failed, or if there is no standard treatment plan, or if standard treatment is not applicable at this stage;
• Efficacy expansion stage: Requirements for different types of tumors are as follows:
• Queue 1: Non small cell lung cancer (NSCLC) Locally advanced, recurrent, or metastatic NSCLC confirmed by histology or cytology, except for subjects known to have other driver genes (including sensitive EGFR mutations, ALK fusion, ROS1 fusion, BRAF V600E mutations, NTRK fusion, RET fusion, etc.); The subject received platinum based treatment on the first line, but did not receive PD-1/PD-L1 inhibitor treatment and had previous treatment failures; Or it may be determined by researchers that first-line platinum based dual therapy is intolerant, but PD-L1 TPS is ≥ 1%; Queue 2: Malignant Solid Tumors of MSI-H/dMMR Subjects with locally advanced, recurrent, or metastatic MSI-H/dMMR malignant solid tumors confirmed by histology or cytology, such as colorectal cancer, head and neck squamous cell carcinoma, etc., will be discussed and determined by the researchers and sponsors based on safety, PK, and efficacy results.
• Queue 3: Based on previous data, determine the tumor type with good therapeutic effect or recommended by the researcher (such as TMB-H) Subjects with locally advanced, recurrent, or metastatic TMB-H malignant solid tumors confirmed by histology or cytology as inoperable will be discussed and determined by the researchers and the sponsor based on safety, PK, and efficacy results.
• All subjects are required to provide tumor tissue samples for PD-L1 testing: tumor tissue samples should preferably be newly obtained. For subjects who cannot provide newly obtained tissue, they can provide tumor tissue samples archived within 3 years before the first study treatment. The sample type should be neutral formalin fixed, paraffin embedded \[FFPE\] tissue blocks or at least 6 unstained tumor tissue sections; If there are less than 6 pieces, it is necessary to consult with the sponsor and obtain their agreement before being allowed to be included in the group;
• ECOG performance status (PS) score 0-1 points;
• Predicted survival period ≥ 3 months
• According to the criteria for evaluating the efficacy of solid tumors (RECIST 1.1), having at least one measurable lesion;
• Having sufficient bone marrow and organ function (without using any blood components and/or cell growth factors within 14 days prior to starting the study treatment):
• Hemoglobin (HB) ≥ 90 g/L; Neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 90 × 109/L； Total bilirubin\<1.5×ULN (for subjects diagnosed with Gilbert syndrome, total bilirubin≤3×ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN (in patients with liver metastases, ALT and/or AST ≤5×ULN)； International normalized ratio (INR) and activated partial thromboplastin (APTT) time≤1.5×ULN; Qualitative analysis of urinary protein≤1+; Or urine protein qualitative≥2+, requiring 24-hour urine protein\<1g
• For male patients whose partners are women of childbearing age, they must agree to abstain from sexual activity for at least 6 months from the signing of the informed consent form until the last administration of the study drug, or to use effective contraception methods. Male patients must also agree not to donate sperm during the same time period;
• The patient voluntarily joined this study, signed an informed consent form, and showed good compliance.

You may not qualify if:

• Subjects with any of the following conditions will not be included in this study:
• Accompanied by untreated or active central nervous system (CNS) tumor metastasis. Subjects with a history of meningeal metastasis or current meningeal metastasis.
• For CNS metastatic subjects, if the CNS tumor has received sufficient local treatment (surgery or radiotherapy); From the end of local treatment to the screening period, no progress was found on imaging examinations; The neurological symptoms of the subjects can be stable for at least 2 weeks before the first medication and do not require glucocorticoid treatment; You can participate in the research;
• Patients with other malignant tumors within the five years prior to the first use of the investigational drug, except for fully treated cervical carcinoma in situ, basal cell or squamous cell carcinoma of the skin, local prostate cancer after radical surgery, ductal carcinoma in situ after radical surgery, and papillary thyroid carcinoma after radical surgery;
• If the researcher determines that the tumor lesion has a tendency to bleed, and the screening imaging examination shows that the subject has imaging evidence of tumor invasion or wrapping around large blood vessels;
• Subjects who have previously used VEGF/PD-1 (PD-L1) bispecific antibodies;
• Have serious cardiovascular and cerebrovascular diseases, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities within 6 months prior to the first use of the investigational drug, such as ventricular arrhythmias requiring clinical intervention, II-III degree atrioventricular block, etc;
• Within 6 months prior to the first use of the investigational drug, acute coronary syndrome, congestive heart failure (NYHA functional class ≥ II), and aortic dissection occurred;
• Within the first 6 months prior to the use of the investigational drug, there have been incidents of arteriovenous thrombosis, such as cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, stroke), deep vein thrombosis, and pulmonary embolism;
• Left ventricular ejection fraction (LVEF)\<50% within 28 days prior to the first use of the investigational drug;
• In a resting state, the mean QTcF obtained from three baseline 12 (or more) lead electrocardiograms is greater than 470 ms for females or greater than 450 ms for males;
• There is uncontrollable pleural effusion, abdominal effusion, or pericardial effusion;
• Patients known or suspected to have interstitial pneumonia; Within three months prior to the first administration, other severe lung diseases that severely affect respiratory function, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans; Non infectious pulmonary inflammation currently requiring steroid treatment;
• Patients who have received immunotherapy in the past and have experienced ≥ grade 3 irAE or ≥ grade 2 immune related myocarditis;

Sponsors & Collaborators

• Convalife (Shanghai) Co., Ltd.: lead

Study Officials

• Jin Li

  Shanghai GoBroad Cancer Hospital China Pharmaceutical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liang Cao

CONTACT

021-6873638; caoliang@convalife.com

Caiqiang Guo

CONTACT

021-6873638; caiqiang.guo@convalife.com

Study Design

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

Model Details: This study is a phase I clinical trial of dose escalation/dose extension/efficacy extension of CVL006 injection monotherapy in patients with advanced solid tumors in a single arm, open label, multicenter manner

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: October 1, 2024
• Study Start: November 20, 2024
• Primary Completion (Estimated): May 20, 2028
• Study Completion (Estimated): November 20, 2028
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share