Trial Title:
Clinical Study of CVL006 Injection in Advanced Solid Tumors
NCT ID:
NCT06621615
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Late stage solid tumor
DLT
MTD
RP2D
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
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
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
CVL006 Injection
Description:
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.
Arm group label:
CVL006 monotherapy group
Other name:
B006
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).
Detailed description:
This study is a phase I clinical trial of single arm, open label, multicenter dose
escalation/dose extension/efficacy extension. The research process for each dose group
includes a screening period (from the signing of the informed consent form by the
subjects to 1 day before the first study medication), a medication period (from the first
study medication to termination of medication), and a follow-up period (90 days after
termination of medication). This study is divided into three stages: I. Dose escalation
stage: Accelerated titration combined with a "3+3" design is used to dose up CVL006
injection. Accelerated titration is preset with three doses, starting at 0.03 mg/kg. Only
one subject is enrolled in each dose group. After completing the three preset doses, four
dose groups are designed according to the "3+3" principle, with 3-6 subjects enrolled in
each dose group, up to a maximum of 42 subjects enrolled. Ib. Dose extension stage: Based
on the observed safety, tolerability, efficacy, and PK characteristics during the dose
escalation process, in the dose group where a certain therapeutic effect is observed in
the subjects (such as 1 PR/CR or 2 SD), the SMC meeting will decide whether to extend the
dose in that dose group. Plan to expand each dose group by no more than 10 subjects
(including subjects with the same dose during the dose escalation phase). And determine
RP2D based on data from dose escalation and expansion stages. Ic. Efficacy expansion
stage: RP2D was selected for expansion, with each tumor type expanded to 10-30 cases.
This study is expected to enroll approximately 100-120 cases, depending on the actual
situation. Dose escalation, dose expansion, and efficacy expansion are the same: CVL006
injection, intravenous infusion, once every 2 weeks, every 28 days as a cycle. The
subsequent administration time is calculated based on the actual date of the previous
CVL006 administration. SMC can adjust the dosing frequency based on safety, tolerability,
and PK results data.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must meet all of the following inclusion criteria in order to be
enrolled in this study
1. Age: 18~75 years old (including both ends), gender not limited;
2. 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.
3. 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;
4. ECOG performance status (PS) score 0-1 points;
5. Predicted survival period ≥ 3 months
6. According to the criteria for evaluating the efficacy of solid tumors (RECIST 1.1),
having at least one measurable lesion;
7. 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
8. Women with fertility must agree to abstain from sexual activity (avoid heterosexual
intercourse) or use effective contraception methods for at least 6 months from the
time of signing the informed consent form until the last administration of the study
drug. And within 7 days before starting the study treatment, the blood HCG test must
be negative and must be non lactating (if the serum pregnancy test is positive,
pregnancy must be ruled out and confirmed with the sponsor before inclusion);
9. 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;
10. The patient voluntarily joined this study, signed an informed consent form, and
showed good compliance.
Exclusion Criteria:
- Subjects with any of the following conditions will not be included in this study:
1. 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;
2. 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;
3. 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;
4. Subjects who have previously used VEGF/PD-1 (PD-L1) bispecific antibodies;
5. Have serious cardiovascular and cerebrovascular diseases, including but not limited
to:
1. 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;
2. 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;
3. 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;
4. Left ventricular ejection fraction (LVEF)<50% within 28 days prior to the first
use of the investigational drug;
5. 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;
6. There is uncontrollable pleural effusion, abdominal effusion, or pericardial
effusion;
7. 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;
8. Patients who have received immunotherapy in the past and have experienced ≥ grade 3
irAE or ≥ grade 2 immune related myocarditis;
9. Patients with active or ever suffered from autoimmune diseases that may recur (such
as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except
patients with clinically stable autoimmune thyroid disease and type I diabetes.
10. Have received systemic corticosteroid (prednisone>10mg/day or equivalent doses of
similar drugs) or other immunosuppressive therapy within 14 days prior to the first
use of the study drug; Excluding the following situations: treatment with topical,
ocular, intra-articular, intranasal, and inhaled corticosteroids; Short term use of
glucocorticoids for preventive treatment (such as preventing contrast agent
allergies).
11. History of esophageal and gastric varices, severe ulcers, unhealed wounds, abdominal
fistulas, abdominal abscesses, or acute gastrointestinal bleeding within 6 months
prior to the first administration; History of gastrointestinal perforation and/or
fistula, gastrointestinal obstruction (including incomplete intestinal obstruction
requiring parenteral nutrition), and extensive intestinal resection (partial
colectomy or extensive small bowel resection) within 6 months prior to the first
administration;
12. Severe infections, including but not limited to bacteremia, severe pneumonia, or
other serious infection complications requiring hospitalization, occurred within 4
weeks prior to the start of the study treatment; Within 2 weeks prior to the first
administration, there is an active infection with CTCAE ≥ 2 that requires
intravenous anti infective treatment;
13. History of immunodeficiency, including HIV testing positive; Presence of active
hepatitis B (HBV DNA higher than the upper limit of normal values in the research
center) or hepatitis C (anti HCV positive and HCV RNA higher than the lower limit of
analysis method detection);
14. Individuals with active pulmonary tuberculosis infection detected through medical
history or CT examination within the year prior to enrollment, or those with a
history of active pulmonary tuberculosis infection more than one year ago but
without formal treatment;
15. Adverse reactions to previous anti-tumor treatments have not yet recovered to a
CTCAE v 5.0 rating of ≤ 1 (except for hair loss, grade 2 peripheral neurotoxicity,
meeting the numerical requirements of the inclusion criteria, or other situations
determined by the researcher to not affect the study drug treatment);
16. Have received chemotherapy within 3 weeks prior to the first use of the
investigational drug, and have received large molecule biologic therapy (including
immunotherapy) or other non marketed clinical investigational drug therapy or other
anti-tumor treatments within 4 weeks prior to the first use of the investigational
drug; Excluding the following:
1. Oral fluorouracil and small molecule targeted drugs should be administered
within 2 weeks before the first use of the investigational drug or within 5
half lives of the drug (whichever is longer);
2. Traditional Chinese medicine with anti-tumor indications should be used 2 weeks
before the first use of the investigational drug;
3. Radical radiotherapy is administered 4 weeks before the first use of the study
drug, while palliative radiotherapy is administered 2 weeks before the first
use of the study drug; During the efficacy expansion phase, those who have been
treated with immune checkpoint agonists (such as CD137 agonists) or immune
checkpoint inhibitors (such as PD-1, PD-L1, etc.) within 6 months prior to the
first use of the investigational drug are not allowed to be enrolled.
18. Have undergone major organ surgery within 4 weeks prior to the first use of the
investigational drug, have experienced significant trauma, or require elective
surgery during the trial period; Perform coarse needle aspiration biopsy or other
minor surgery within 7 days before the first medication (excluding central venous
catheterization and infusion port implantation); 19. Within 4 weeks before the first
administration, there is a history of bleeding tendency or coagulation disorders
and/or clinically significant bleeding symptoms or risks, including but not limited
to: a Gastrointestinal bleeding; b. Hemoptysis (coughing up ≥ 15ml of fresh blood or
blood clots); c. Nasal bleeding/epistaxis; d. Receive therapeutic anticoagulant
therapy before the first administration; 20. History of hypertensive crisis or
hypertensive encephalopathy in the past; Within one month before the first
administration, there is hypertension and the systolic blood pressure is ≥ 150mmHg
or diastolic blood pressure is ≥ 100mmHg after oral antihypertensive medication; 21.
Active or previous history of inflammatory bowel disease (such as Crohn's disease,
ulcerative colitis, or chronic diarrhea); 22. Known history of allogeneic organ
transplantation or allogeneic hematopoietic stem cell transplantation; 23. Known to
have a history of severe allergic reactions to multiple medications; 24. Receive
live virus vaccine 30 days before the first administration, or plan to receive live
vaccine during the study period; According to the researchers' assessment, there are
other factors that may affect the research results or force the termination of this
study, such as alcohol abuse, drug abuse, other serious illnesses (including mental
illnesses) that require concomitant treatment, severe abnormal laboratory test
values, family or social factors, and other situations that may affect the safety of
the subjects or the collection of experimental data.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
November 20, 2024
Completion date:
November 20, 2028
Lead sponsor:
Agency:
Convalife (Shanghai) Co., Ltd.
Agency class:
Industry
Source:
Convalife (Shanghai) Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06621615
