Non-small Cell Lung CancerPhase 2NCT06277674
Efficacy of Cadonilimab in Non-squamous Non-small Cell Lung Cancer Patients Resistant to EGFR-TKI
A Phase 2 study testing Cadonilimab plus Pemetrexed and Anlotinib in people with Non-small Cell Lung Cancer, run by Guangzhou University of Traditional Chinese Medicine at 1 site in China.
Trial summary
This study was designed to evaluate the efficacy and safety of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) in combination with pemetrexed and anlotinib for treatment of elderly patients with T790M-negative advanced non-squamous non-small cell lung cancer following resistance to EGFR-TKI. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Cadonilimab plus Pemetrexed and Anlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 2 Nov 2023to Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients signed informed consent, willing to accept this regimen, able to adhere to the medication, and had good compliance.
- Patients with advanced or metastatic non-small cell lung cancer (stage IIIB, IIIC, or IV according to the AJCC staging system, 8th edition) diagnosed by histopathology or cytopathology
- Histologically or cytologically confirmed, locally advanced or metastatic nonsquamous non-small-cell lung cancer (stage IIIB, IIIC, or IV according to the AJCC staging manual, 8th edition) patients with EGFR sensitive mutations (confirmed by tumour histology, cytology, or cell-free or circulating tumour DNA) progressed after receiving EGFR tyrosine-kinase inhibitor therapy; confirmed EGFR Thr790Met negative mutation status after receiving first-generation, second-generation or third-generation EGFR tyrosine-kinase inhibitor as first-line or second-line treatment
- Eastern Cooperative Oncology Group performance status of 0 to 2
- Presence of at least one measurable lesion
- An estimated life expectancy of at least 3 months
- Good organ function was defined as hemoglobin≥90g/L (no blood transfusion within 7 days), absolute neutrophil count ≥1.5×109/L, and platelet count≥100×109/L. Total bilirubin level≤1.5 times of the upper limit of normal value (ULN), albumin ≥30g/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times of upper limit of normal (ULN), in cases with liver metastasis, AST and ALT≤5 times of ULN; Creatinine ≤1.5 times of ULN; International normalized ratio (INR) or prothrombin time (PT) ≤1.5 times of ULN, if the participant is receiving anticoagulant therapy normally, as long as the PT is within the prescribed range of anticoagulant drugs
Who cannot join
- Concomitant driver mutations for which there were known therapies were identified, including but not limited to ALK rearrangement, ROS1 fusion, or BRAF V600E mutation
- Previously received systemic anti-tumour therapy (including cytotoxic chemotherapy and antiangiogenic therapy) except EGFR tyrosine-kinase inhibitors for advanced NSCLC
- Previously received immunotherapy (including anti-PD-1, anti-PD-L1, or anti-CTLA-4) antibodies or agents
- The presence of an active malignancy within 2 years prior to the first dose was not allowed. Participants with locally cured tumors, such as basal-cell carcinoma or squamous-cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the breast, were not excluded
- The enrollment of another clinical study was excluded except for observational or noninterventional studies or interventional studies with a follow-up period exceeding four weeks after the last dose of the study drug or more than five half-lives of the study drug
- Patients received systemic treatment with Chinese patent medicine or Chinese herbal medicine exhibiting anti-tumor properties or immunomodulatory drugs (such as thymosin, interferon, interleukin) indicated for anti-tumor purposes within a 2-week period prior to the initial dosage
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- Participants with an active, known, or suspected autoimmune disease or a history of autoimmune disease are excluded from the study, except for those with Vitiligo, alopecia, Graves' disease, psoriasis, or eczema that do not require systemic treatment for nearly 2 years. Additionally, Participants with asymptomatic hypothyroidism (due to autoimmune thyroiditis) or stable doses of hormone replacement therapy and type I diabetes requiring only stable doses of insulin replacement therapy are also exempted. Furthermore, participants who had childhood asthma that has completely resolved and no longer require any intervention in adulthood or whose disease does not recur without an external trigger are eligible for inclusion
- Participants who have received systemic treatment with corticosteroids (prednisone equivalent dose > 10 mg/day) or other immunosuppressive drugs within 14 days prior to the first dose are excluded
- Documented history of immunodeficiency
- Documented history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
- Major surgical procedures (such as laparotomy, thoracotomy, viscerectomy, etc.) or severe trauma within 28 days prior to the initial administration (intravenous drip replacement is acceptable); Surgery aimed at improving or reducing the risk of oncologic complications within 14 days before the first dose; Or incomplete recovery from any of the aforementioned previous surgeries. Major surgical procedures were planned (at the investigator's discretion) within 30 days after the initial dose. Local surgery (e.g., placement of systemic ports, core needle biopsy) was permitted if performed at least 24 hours prior to initiation of study treatment
- Patients with a medical history of gastrointestinal perforation, gastrointestinal fistula, or female genital fistula (such as vesicovaginal fistula, urethrovaginal fistula, etc.) within the past 6 months prior to the initial drug administration were eligible for enrollment if the perforation or fistula had been surgically treated (e.g., excision or repair) and if complete recovery or resolution of the condition was confirmed by the investigator
- The presence of interstitial lung disease, whether symptomatic or not, may hinder the detection or management of suspected drug-related pulmonary toxicity
- The presence of active pulmonary tuberculosis (TB). Patients suspected to have active TB underwent examination through chest X-ray and sputum analysis, while being assessed for clinical signs and symptoms
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Guangdong Provincial Hospital of Traditional Chinese Medicine
Guangzhou, Guangdong, 510120
Haibo Zhang, Prof, 86-020-81887233 ext. 34830, haibozh@gzucm.edu.cn
About this study
Official title: A Phase II Clinical Trial Evaluating the Efficacy of Cadonilimab in Combination With Pemetrexed and Anlotinib for Treatment of Elderly Patients With T790M-negative Advanced Non-squamous Non-small Cell Lung Cancer Following Resistance to EGFR-TKI.
This study was designed to evaluate the efficacy and safety of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) in combination with pemetrexed and anlotinib for treatment of elderly patients with T790M-negative advanced non-squamous non-small cell lung cancer following resistance to EGFR-TKI.
Read the detailed description
This prospective study aims to enroll 20 elderly patients (age≥65 years) with advanced non-squamous NSCLC with T790M negative after EGFR-TKI resistance. Eligible patients will be given 4 to 6 cycles of cadonilimab plus pemetrexed and anlotinib, followed by maintenance treatment with cadonilimab plus anlotinib until disease progression, intolerable toxicity, withdrawal of consent, death, or other protocol-specified causes, whichever occurs first. Imaging assessments are scheduled to conduct every 6 weeks for the first year and then every 12 weeks thereafter. The follow-up of participants who discontinued treatment for reasons unrelated to disease progression will be continued, until the initiation of other anti-tumor therapy, disease progression, death, or the end of the study, whichever occurrs first.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Cadonilimab plus Pemetrexed and Anlotinib
- Keywords
- Cadonilimab, Immune checkpoint inhibitors, EGFR-TKI resistance, elderly non-small cell lung cancer patients
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cadonilimab plus Pemetrexed and AnlotinibDrug
Also called ICIs in combination with chemotherapy and antiangiogenic therapy
Cadonilimab was administered intravenously at a dose of 10 mg/kg every 3 weeks. Pemetrexed was administered intravenously at a dose of 500 mg/m² every 3 weeks Anlotinib was taken at doses of 10mg orally once daily for two weeks on a one-week-off schedule.
| Study group | Role | What they receive |
|---|---|---|
| cadonilimab plus pemetrexed and anlotinib | Experimental | Twenty elderly patients (age≥65 years) with advanced non-squamous NSCLC with T790M negative after EGFR-TKI resistance will be enrollrd in this study. Participants will receive 4 to 6 cycles of cardunnilumab in combination with pemetrexed and anlotinib every 3 weeks, followed by maintenance treatment with cadonilimab plus anlotinib until disease progression, intolerable toxicity, withdrawal of consent, death, or other protocol-specified causes, whichever occurs first.
Cadonilimab was administered intravenously at a dose of 10 mg/kg every 3 weeks. Pemetrexed was administered intravenously at a dose of 500 mg/m² every 3 weeks Anlotinib was taken at doses of 10mg orally once daily for two weeks on a one-week-off schedule. Receives: Drug: Cadonilimab plus Pemetrexed and Anlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR(Objective response rate)
ORR (overall response rate) is defined as sum of complete response (CR) rate and partial response (PR) rate, according to RECIST v 1.1, based on the chest, abdomen and/or brain CT/MRI evaluation. Patients will undergo a follow-up imaging examination every 6 weeks for the first year and then every 12 weeks thereafter.
Measured: From date of randomization until the date of death or date of withdraw, whichever came first, assessed up to 120 months
Secondary outcomes (3)
Progression-free survival (PFS)
The time from the date of randomization to the date of disease progression, date of withdraw, or death from any cause, whichever occurs first.
Measured: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months.
(Disease control rate assessed by investigators) DCR (CR+PR+SD)
DCR (disease control rate) is defined as sum of complete response (CR) rate, partial response (PR) rate and stable disease (SD) rate, according to RECIST v 1.1, based on the chest, abdomen and/or brain CT/MRI evaluation. Patients will undergo a follow-up imaging examination every 6 weeks for the first year and then every 12 weeks thereafter.
Measured: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months
Overall survival (OS)
The time from the date of randomization to the date of withdraw or date of death from any cause, whichever occurs first
Measured: From date of randomization to the date of withdraw or date of death from any cause, whichever occurs first, assessed up to 120 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2024
- Study start2 Nov 2023
- Primary completionDec 2024 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou University of Traditional Chinese Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Akeso Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Haibo Zhang, Guangzhou University of Traditional Chinese Medicine
- Investigators
- Haibo Zhang, Prof, Principal investigator, Guangdong Provincial Hospital of Traditional Chinese Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06277674
- Sponsor's protocol ID
- ZF2023-252
- Status last verified
- Mar 2024
- First submitted
- 18 Feb 2024
- Last updated
- 8 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial Evaluating the Efficacy of Cadonilimab in Combination With Pemetrexed and Anlotinib for Treatment of Elderly Patients With T790M-negative Advanced Non-squamous Non-small Cell Lung Cancer Following Resistance to EGFR-TKI.
- ClinicalTrials.gov ID
- NCT06277674
- Acronym / sponsor ID
- ZF2023-252
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Cadonilimab, Immune checkpoint inhibitors, EGFR-TKI resistance, elderly non-small cell lung cancer patients
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Guangzhou University of Traditional Chinese MedicineUniversity, hospital or other
- Collaborators
- Akeso Pharmaceuticals, Inc.
- Study start
- 2 Nov 2023 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 26 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was designed to evaluate the efficacy and safety of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) in combination with pemetrexed and anlotinib for treatment of elderly patients with T790M-negative advanced non-squamous non-small cell lung cancer following resistance to EGFR-TKI.
Detailed description
This prospective study aims to enroll 20 elderly patients (age≥65 years) with advanced non-squamous NSCLC with T790M negative after EGFR-TKI resistance. Eligible patients will be given 4 to 6 cycles of cadonilimab plus pemetrexed and anlotinib, followed by maintenance treatment with cadonilimab plus anlotinib until disease progression, intolerable toxicity, withdrawal of consent, death, or other protocol-specified causes, whichever occurs first. Imaging assessments are scheduled to conduct every 6 weeks for the first year and then every 12 weeks thereafter. The follow-up of participants who discontinued treatment for reasons unrelated to disease progression will be continued, until the initiation of other anti-tumor therapy, disease progression, death, or the end of the study, whichever occurrs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cadonilimab plus pemetrexed and anlotinib | Experimental | Drug: Cadonilimab plus Pemetrexed and AnlotinibTwenty elderly patients (age≥65 years) with advanced non-squamous NSCLC with T790M negative after EGFR-TKI resistance will be enrollrd in this study. Participants will receive 4 to 6 cycles of cardunnilumab in combination with pemetrexed and anlotinib every 3 weeks, followed by maintenance treatment with cadonilimab plus anlotinib until disease progression, intolerable toxicity, withdrawal of consent, death, or other protocol-specified causes, whichever occurs first. Cadonilimab was administered intravenously at a dose of 10 mg/kg every 3 weeks. Pemetrexed was administered intravenously at a dose of 500 mg/m² every 3 weeks Anlotinib was taken at doses of 10mg orally once daily for two weeks on a one-week-off schedule. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (7 listed)
- Patients signed informed consent, willing to accept this regimen, able to adhere to the medication, and had good compliance.
- Patients with advanced or metastatic non-small cell lung cancer (stage IIIB, IIIC, or IV according to the AJCC staging system, 8th edition) diagnosed by histopathology or cytopathology
- Histologically or cytologically confirmed, locally advanced or metastatic nonsquamous non-small-cell lung cancer (stage IIIB, IIIC, or IV according to the AJCC staging manual, 8th edition) patients with EGFR sensitive mutations (confirmed by tumour histology, cytology, or cell-free or circulating tumour DNA) progressed after receiving EGFR tyrosine-kinase inhibitor therapy; confirmed EGFR Thr790Met negative mutation status after receiving first-generation, second-generation or third-generation EGFR tyrosine-kinase inhibitor as first-line or second-line treatment
- Eastern Cooperative Oncology Group performance status of 0 to 2
- Presence of at least one measurable lesion
Key exclusion criteria (14 listed)
- Concomitant driver mutations for which there were known therapies were identified, including but not limited to ALK rearrangement, ROS1 fusion, or BRAF V600E mutation
- Previously received systemic anti-tumour therapy (including cytotoxic chemotherapy and antiangiogenic therapy) except EGFR tyrosine-kinase inhibitors for advanced NSCLC
- Previously received immunotherapy (including anti-PD-1, anti-PD-L1, or anti-CTLA-4) antibodies or agents
- The presence of an active malignancy within 2 years prior to the first dose was not allowed. Participants with locally cured tumors, such as basal-cell carcinoma or squamous-cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the breast, were not excluded
- The enrollment of another clinical study was excluded except for observational or noninterventional studies or interventional studies with a follow-up period exceeding four weeks after the last dose of the study drug or more than five half-lives of the study drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cadonilimab plus Pemetrexed and AnlotinibAlso: ICIs in combination with chemotherapy and antiangiogenic therapyCadonilimab was administered intravenously at a dose of 10 mg/kg every 3 weeks. Pemetrexed was administered intravenously at a dose of 500 mg/m² every 3 weeks Anlotinib was taken at doses of 10mg orally once daily for two weeks on a one-week-off schedule. | Drug | cadonilimab plus pemetrexed and anlotinib |
Primary outcome
ORR(Objective response rate)
Time frame: From date of randomization until the date of death or date of withdraw, whichever came first, assessed up to 120 months
ORR (overall response rate) is defined as sum of complete response (CR) rate and partial response (PR) rate, according to RECIST v 1.1, based on the chest, abdomen and/or brain CT/MRI evaluation. Patients will undergo a follow-up imaging examination every 6 weeks for the first year and then every 12 weeks thereafter.
3 secondary outcomes
Progression-free survival (PFS)
Time frame: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months.
(Disease control rate assessed by investigators) DCR (CR+PR+SD)
Time frame: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months
Overall survival (OS)
Time frame: From date of randomization to the date of withdraw or date of death from any cause, whichever occurs first, assessed up to 120 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Haibo Zhang, Prof principal investigator
Guangdong Provincial Hospital of Traditional Chinese Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cadonilimab plus Pemetrexed and Anlotinib in people with Non-small Cell Lung Cancer, run by Guangzhou University of Traditional Chinese Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fangfang Hou, Dr (86-020-81887233 ext. 34830, 13527816095@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR(Objective response rate) (time frame: From date of randomization until the date of death or date of withdraw, whichever came first, assessed up to 120 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.