Cadonilimab in Patients (Pts) With Advanced Non-small Cell Lung Cancer (NSCLC)

NCT05816499 | Active Not Recruiting Phase 1

• 1 other identifier: AK104-IIT-018
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

NSCLC Stage IV; NSCLC Stage IIIB; NSCLC Stage IIIC

Keywords

Cadonilimab; AK104; NSCLC; resistance

Outcome Measures

Primary Outcomes (2)

• RP2D of anlotinib

  Will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Overall toxicity incidence as well as toxicity profiles will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. Proportion of acute and late toxicity will be reported, and 95% confidence intervals will be estimated using the Clopper-Pearson method.

  Up to 21 days after the first cycle of study treatment

• 6-month progression-free survival (PFS) rate

  Will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be reported and its 95% confidence intervals will be estimated using the Clopper-Pearson method. PFS rates of two patient groups stratified by binary biomarker (PD-L1 and KRAS status), respectively will be estimated with the Kaplan-Meier method and compared using the log-rank test, respectively. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of PD-L1 and KRAS status on the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.

  up to 6 months

Secondary Outcomes (4)

• Overall response rate

  Through study completion, an average of 1 year

• Overall survival (OS)

  up to 10 years

• Investigator assessed-progression-free survival (IA-PFS)

  From date of sub-study registration to date of first documentation of progression assessed by central review or symptomatic deterioration, or death due to any cause, assessed up to 3 years

• Incidence of adverse events

  Up to 30 days after the last dose of study treatment

Study Arms (1)

Arm A (cadonilimab，anlotinib，docetaxel )

EXPERIMENTAL

Patients receive anlotinib 6mg/8mg/10mg qd 2W/3W and cadonilimab IV over 90 minutes on day 1. Patients also receive docetaxel 60-75 mg/m2 IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Cadonilimab; Drug: Anlotinib; Drug: Docetaxel

Interventions

Cadonilimab DRUG

Given IV, 10mg/kg Q3W

Also known as: AK104

Arm A (cadonilimab，anlotinib，docetaxel )

Anlotinib DRUG

oral，6mg/8mg/10mg qd 2W/3W

Also known as: AL3818

Arm A (cadonilimab，anlotinib，docetaxel )

Docetaxel DRUG

Given IV, 60-75mg/m2 Q3W

Also known as: Docetaxel Trihydrate, Docetaxel Hydrate, Taxoltere Metro, RP 56976, RP-56976, RP56976, Docetaxel Anhydrous, N-Debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol, N Debenzoyl N tert butoxycarbonyl 10 deacetyltaxol, NSC 628503, Taxotere

Arm A (cadonilimab，anlotinib，docetaxel )

Eligibility Criteria

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

You may qualify if:

• Age≥18 years old
• 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
• 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)
• Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, and ROS 1 gene rearrangement, and BRAF V600E mutation.
• 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
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Life expectancy \> 12 weeks as determined by the investigator
• Patients must have at least one measurable lesion (as defined by RECIST v1.1), which is suitable for repeated and accurate measurement
• Absolute neutrophil count (ANC) ≥ 1500/uL (collected within 10 days prior to the start of study treatment)
• Platelets ≥ 100 000/uL (collected within 10 days prior to the start of study treatment)
• Hemoglobin ≥ 9.0 g/dL (collected within 10 days prior to the start of study treatment)
• Creatinine clearance \[CrCl\]) ≥ 50 mL/min(Creatinine clearance (CrCl) should be calculated per institutional standard)
• Total bilirubin ≤ 1.5 x ULN (collected within 10 days prior to the start of study treatment)
• 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
• Serum albumin(ALB)≥28 g/L

You may not qualify if:

• 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（CD272）、VISTA（B7-H5）、LIGHT（CD258）、B7-H3（CD276）、 B7-H4（VTCN1）、HVEM、CD80/CD86、MHC Ⅱ、GAL9、IDO、PVR（CD155）、Nectin-2（CD112）.
• Patients have prior exposure to docetaxel, anlotinib, lenvatinib, apatinib, cabozantinib.
• The last systemic anti-tumor treatment (chemotherapy, immunotherapy, biological agents, anti-angiogenic drugs, etc.) was received within 3 weeks before the first administration.
• 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).
• Patients with explosive progress.
• 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.
• 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.
• Patients can not swallow pills, with malabsorption syndrome, or any condition that affects gastrointestinal absorption;
• Patients with active or previous history of inflammatory bowel disease (such as Crohn's disease, ulcerative colitis or chronic diarrhea).
• Patients have a history of immune deficiency, with HIV antibody test positive or use systemic corticosteroids or other immunosuppressants for a long time.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead
• The Affiliated Hospital of Qingdao University: collaborator
• Anhui Provincial Hospital: collaborator
• Zhejiang University: collaborator

Study Sites (5)

lejie Cao

Hefei, Anhui, 230000, China

Location

Jing Wang

Qingdao, Shandong, 266000, China

Location

Zhuang Yu

Qingdao, Shandong, 266000, China

Location

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200000, China

Location

Jianya Zhou

Hangzhou, Zhejiang, 310000, China

Location

Related Publications (1)

• Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011 Feb;6(2):244-85. doi: 10.1097/JTO.0b013e318206a221.

  PMID: 21252716 BACKGROUND

Related Links

• 2021 ESMO Abstract #1191O
• 2021 ESMO Abstract #1284P

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

anlotinib; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Baohui Han, M.D

  ShanghaiChest Hospital

  STUDY CHAIR

• Jianya Zhou, M.D

  Zhejiang University

  PRINCIPAL INVESTIGATOR

• Zhuang Yu, M.D

  The Affiliated Hospital of Qingdao University

  PRINCIPAL INVESTIGATOR

• Jing Wang, M.D

  The Affiliated Hospital of Qingdao University

  PRINCIPAL INVESTIGATOR

• lejie Cao, M.D

  Anhui Provincial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: 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: March 1, 2023
• First Posted: April 18, 2023
• Study Start: February 16, 2023
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2025
• Last Updated: June 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: starting 6 months after publication

Locations

CN (5)