Trial Title:
Cadonilimab in Patients (Pts) With Advanced Non-small Cell Lung Cancer (NSCLC)
NCT ID:
NCT05816499
Condition:
NSCLC Stage IV
NSCLC Stage IIIB
NSCLC Stage IIIC
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Docetaxel
Conditions: Keywords:
Cadonilimab
AK104
NSCLC
resistance
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab
Description:
Given IV, 10mg/kg Q3W
Arm group label:
Arm A (cadonilimab，anlotinib，docetaxel )
Other name:
AK104
Intervention type:
Drug
Intervention name:
Anlotinib
Description:
oral，6mg/8mg/10mg qd 2W/3W
Arm group label:
Arm A (cadonilimab，anlotinib，docetaxel )
Other name:
AL3818
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Given IV, 60-75mg/m2 Q3W
Arm group label:
Arm A (cadonilimab，anlotinib，docetaxel )
Other name:
Docetaxel Trihydrate
Other name:
Docetaxel Hydrate
Other name:
Taxoltere Metro
Other name:
RP 56976
Other name:
RP-56976
Other name:
RP56976
Other name:
Docetaxel Anhydrous
Other name:
N-Debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol
Other name:
N Debenzoyl N tert butoxycarbonyl 10 deacetyltaxol
Other name:
NSC 628503
Other name:
Taxotere
Summary:
This phase Ib/II trial studies how well cadonilimab combined with anlotinib and docetaxel
work in treating patients with non-small cell lung cancer that is stage IV or has come
back. Cadonilimab, a PD-1/CTLA-4 bispecific antibody, may help the body's immune system
attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Anlotinib can regulate tumor microenvironment. Docetaxel was used in standard of care
chemotherapy for non-small cell lung cancer, work to stop the growth of tumor cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving cadonilimab, anlotinib and docetaxel together may work better in
treating patients with non-small lung cancer compared to standard of care.
Detailed description:
PRIMARY OBJECTIVES:
1. Dose discovery stage: evaluate the safety of cadonilimab combined with anlotinib and
docetaxel in the treatment of locally advanced and metastatic NSCLC after failure of
treatment with PD-L1/1 inhibitors and the recommended dose of anlotinib.
2. Dose expansion stage: evaluate the 6-month PFS rate of patients with locally
advanced and metastatic NSCLC after failure of treatment with PD-L1/1 inhibitors by
cadonilimab combined with anlotinib and docetaxel, which was evaluated by
researchers based on RECIST v1.1.
SECONDARY OBJECTIVES:
1. evaluate the objective response rate (ORR), progression-free survival (PFS), disease
control rate (DCR), duration of response (DoR), time to response (TTR), and total
survival (OS) of patients with locally advanced and metastatic NSCLC after failure
of treatment with PD-L1/1 inhibitors with cadonilimab, anlotinib, and docetaxel.
2. evaluate the safety and tolerability of cadonilimab combined with arotinib and
docetaxel in the treatment of locally advanced and metastatic NSCLC after failure of
treatment with PD-L1/1 inhibitor.
OUTLINE:
This is a prospective, open, single-arm, multi-center, phase I b/II clinical study. All
patients were confirmed Locally advanced (stage IIIB/IIIC) that cannot be resected by
radical surgery and cannot accept radical synchronous/sequential radiotherapy and
chemotherapy or metastatic (stage IV) NSCLC by histology or cytology. Patients must have
progressed on at most a PD-1/L1 inhibitor and a platinum-based chemotherapy (combined or
sequential, regardless of sequence), and at least two cycles of PD-1/L1 inhibitor
(combined or non-combined chemotherapy) with clinical benefits (PFS ≥ 3 months). The
study is divided into two parts. The first part is the dose discovery stage. The patients
will receive a 21-day observation period of dose limiting toxicity (DLT). 3-6 subjects
will be enrolled in each dose, and finally evaluate the safety and determine the
recommended dose (RP2D) for phase II clinical study according to the "3+3" principle. We
will continue to recruit 44 patients at the dose expansion stage.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age≥18 years old
2. Locally advanced (stage IIIB/IIIC) that cannot be resected by radical surgery and
cannot accept radical synchronous/sequential radiotherapy and chemotherapy and
metastatic (stage IV) NSCLC confirmed by histology or cytology
3. Patients must have progressed on at most a PD-1/L1 inhibitor and a platinum-based
chemotherapy (combined or sequential, regardless of sequence), and at least two
cycles of PD-1/L1 inhibitor (combined or non-combined chemotherapy) with clinical
benefits (PFS ≥ 3 months)
4. Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK gene
fusion, and ROS 1 gene rearrangement, and BRAF V600E mutation.
5. Has measurable disease based on Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1. Lesions situated in a previously irradiated area are considered
measurable if progression has been demonstrated in such lesions
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
7. Life expectancy > 12 weeks as determined by the investigator
8. Patients must have at least one measurable lesion (as defined by RECIST v1.1), which
is suitable for repeated and accurate measurement
9. Absolute neutrophil count (ANC) ≥ 1500/uL (collected within 10 days prior to the
start of study treatment)
10. Platelets ≥ 100 000/uL (collected within 10 days prior to the start of study
treatment)
11. Hemoglobin ≥ 9.0 g/dL (collected within 10 days prior to the start of study
treatment)
12. Creatinine clearance [CrCl]) ≥ 50 mL/min(Creatinine clearance (CrCl) should be
calculated per institutional standard)
13. Total bilirubin ≤ 1.5 x ULN (collected within 10 days prior to the start of study
treatment)
14. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤
2.5 x ULN (≤ 5 x ULN for participants with liver metastases) (collected within 10
days prior to the start of study treatment
15. Serum albumin(ALB)≥28 g/L
16. International standardized ratio (INR) and activated partial thrombin time (APTT) ≤
1.5 × ULN
17. Left ventricular ejection fraction (LVEF) ≥ 50%
18. A male participant must agree to use a contraception during the treatment period
plus an additional 120 days after the last dose of study treatment and refrain from
donating sperm during this period
19. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) OR
2. A WOCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 120 days plus 30 days (a menstruation cycle) after the
last dose of study treatment
Exclusion Criteria:
1. Previously received treatment for tumor immune mechanism other than any anti-PD-1/L1
inhibitor for advanced NSCLC stage, such as
CTLA-4（CD152）、TIGIT、OX-40、CD137、ICOS、CD40、CD47、CD73、GITR、TOX、LAG-3、TIM3、SIRPα、BTLA（C
D272）、VISTA（B7-H5）、LIGHT（CD258）、B7-H3（CD276）、 B7-H4（VTCN1）、HVEM、CD80/CD86、MHC
Ⅱ、GAL9、IDO、PVR（CD155）、Nectin-2（CD112）.
2. Patients have prior exposure to docetaxel, anlotinib, lenvatinib, apatinib,
cabozantinib.
3. The last systemic anti-tumor treatment (chemotherapy, immunotherapy, biological
agents, anti-angiogenic drugs, etc.) was received within 3 weeks before the first
administration.
4. The following treatments were received within 2 weeks before the first
administration: TKI treatment, hormone anti-tumor treatment, palliative local
treatment for non-target lesions Non-specific immunomodulatory therapy (such as
interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 for
thrombocytopenia).
5. Patients with explosive progress.
6. Patients with other active malignant tumors except for NSCLC within 3 years before
enrollment. Patients with other malignant tumors that have been cured by local
treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder
cancer cancer, cervical or breast cancer in situ, are not excluded.
7. Patients with active autoimmune diseases that require systemic treatment in the past
two years (such as the use of disease improvement drugs, corticosteroids,
immunosuppressants) (excluding irAE caused by the use of PD-1/L1 inhibitors).
Replacement therapy (such as thyroid hormone, insulin, or physiological
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not
considered as a systemic treatment.
8. Patients can not swallow pills, with malabsorption syndrome, or any condition that
affects gastrointestinal absorption;
9. Patients with active or previous history of inflammatory bowel disease (such as
Crohn's disease, ulcerative colitis or chronic diarrhea).
10. Patients have a history of immune deficiency, with HIV antibody test positive or use
systemic corticosteroids or other immunosuppressants for a long time.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
lejie Cao
Address:
City:
Hefei
Zip:
230000
Country:
China
Facility:
Name:
Jing Wang
Address:
City:
Qingdao
Zip:
266000
Country:
China
Facility:
Name:
Zhuang Yu
Address:
City:
Qingdao
Zip:
266000
Country:
China
Facility:
Name:
Shanghai Chest Hospital
Address:
City:
Shanghai
Zip:
200000
Country:
China
Facility:
Name:
Jianya Zhou
Address:
City:
Hangzhou
Zip:
310000
Country:
China
Start date:
February 16, 2023
Completion date:
December 30, 2025
Lead sponsor:
Agency:
Shanghai Chest Hospital
Agency class:
Other
Collaborator:
Agency:
The Affiliated Hospital of Qingdao University
Agency class:
Other
Collaborator:
Agency:
Anhui Provincial Hospital
Agency class:
Other
Collaborator:
Agency:
Zhejiang University
Agency class:
Other
Source:
Shanghai Chest Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05816499
https://www.esmo.org/
https://www.esmo.org/
