Non Small Cell Lung CancerPhase 1SEQUENCENCT03527251
Anti-CTLA-4 Antibody Followed by Anti-PD-1 Antibody in Recurrent or Metastatic NSCLC
A Phase 1 study testing Ipilimumab and SHR-1210 in people with Non Small Cell Lung Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
Immunotherapy has made rapid progress in melanoma, Hodgkin's lymphoma, non-small cell lung cancer, and bladder cancer, etc. Preclinical data suggested that the use of anti-PD-1 antibody in combination with CTLA-4 receptor blockers may increase antitumor activity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Ipilimumab and SHR-1210
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 15 May 2018to 31 Dec 2019
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >=18 years old, male or female;
- Histologically confirmed locally advanced or metastatic non-small-cell lung cancer;
- At least one systemic chemotherapy regimen for locally advanced or metastatic disease (patients received neoadjuvant chemotherapy, concurrent chemoradiotherapy, or adjuvant chemotherapy within 6 months can be considered as first-line system therapy);
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
- At least one measurable lesion according to criteria RECIST v1.1;
- Life expectancy of at least 12 weeks;
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- Patient has adequate bone marrow as defined by the following laboratory values:
- White blood cell ≥ 3.0 × 109/L Absolute neutrophil count ≥ 1.5 × 109/L Platelets ≥ 75 × 109/L
- Patient has adequate organ function as defined by the following laboratory values:
- In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver metastases, ALT and AST should be < 5 × ULN Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range of the central laboratory in patients with well documented Gilbert's Syndrome Serum creatinine ≤ 1.5 × ULN
- Provide written, informed consent to participate in the study and follow the study procedures;
- Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, ie, intrauterine device, bilateral tubal ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle of the patient), from the time of informed consent until 28 days after the last dose of the investigational products. Men and their female partners of childbearing potential must agree and commit to use a highly effective method of contraception (ie, any of the above methods or hormonal contraception associated with inhibition of ovulation) while on treatment and for 3 months after last dose of investigational products
Who cannot join
- Driver gene EGFR, ALK and ROS were positive;
- In presence of active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Patients with hormone replacement therapy can be included; Patients with vitiligo or asthma in childhood have been completely relieved, and no intervention in adults can be included; The subjects who needed medical intervention with bronchial dilation were ineligible;
- Patients are using immunity inhibitors or systemic hormone therapy for immunosuppression purpose (such as prednisone > 10 mg/day), except for local hormone therapy.
- Patients were known to be allergic to macromolecular protein, or any components in ipilimumab or SHR-1210;
- Patients with clinical symptoms of central nervous system metastasis (e.g. brain edema, requirement of hormone intervention, or brain metastases progression);
- Another malignancy within 2 years prior to screening, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer;
- Patients with congenital or acquired immunodeficiency (such as HIV infection), or active hepatitis (HBV DNA≥10⁴/ml);
- Any severe and / or uncontrolled medical conditions.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Cancer Center of Sun-Yat Sen University (CCSYSU)
Guangzhou, Guangdong, 510060
Li Zhang, Master, 86-20-8734-3458, zhangli6@mail.sysu.edu.cn
About this study
Official title: A Phase I Study Evaluating the Safety and Efficacy of CTLA-4 Antibody Ipilimumab Followed by PD-1 Antibody SHR-1210 in Patients With Recurrent or Metastatic Non-small Cell Lung Cancer
Immunotherapy has made rapid progress in melanoma, Hodgkin's lymphoma, non-small cell lung cancer, and bladder cancer, etc. Preclinical data suggested that the use of anti-PD-1 antibody in combination with CTLA-4 receptor blockers may increase antitumor activity. The CheckMate-012 study showed that nivolumab and ipilimumab combination therapy achieved an overall response rate of 43% in unselected patients with non-small cell lung cancer, compared with 23% in the nivolumab monotherapy group; and in the PD-L1 positive subgroup, nivolumab in combination with ipilimumab showed a response rate of 57%, while nivolumab alone was 28%. This showed that the combination therapy of nivolumab and ipilimumab can increase the efficacy, but the adverse events of grade 3 or above of combination therapy reach 37%. The toxic side effects limit the widespread use of nivolumab in combination with ipilimumab therapy.
However, since the action of ipilimumab is limited to the initiation of the immune response (antigen presentation and immune cell activation), and its long half-time of 15.4 days, ipilimumab can used as an induction therapy, following by the PD1 monoclonal antibody. This phase I study is aimed to evaluated the safety and efficacy of CTLA-4 antibody followed by PD-1 antibody in patients with recurrent or metastatic non-small cell lung cancer.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Ipilimumab, SHR-1210
- Keywords
- clinical trial, phase I, CTLA-4 antibody, PD-1 antibody, non-small cell lung cancer
- 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.
IpilimumabDrug
Also called Yervoy
Patients received two doses of intravenous ipilimumab (at a dose of 1 mg per kilogram of body weight) every 3 weeks, following by intravenous SHR-1210 (at a fixed dose of 200mg) every 2 weeks.
SHR-1210Drug
Patients received two doses of intravenous ipilimumab (at a dose of 1 mg per kilogram of body weight) every 3 weeks, following by intravenous SHR-1210 (at a fixed dose of 200mg) every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Sequential group | Experimental | intravenous ipilimumab following by intravenous SHR-1210 Receives: Drug: Ipilimumab; Drug: SHR-1210 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety in the treatment of ipilimumab followed by SHR1210
Adverse events occurring up to 30 days after the last dose of ipilimumab or SHR1210 are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
Measured: 24 months
Secondary outcomes (6)
Overall Response Rate (ORR)
ORR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measured: Up to 4 weeks
Clinical Benefit Response (CBR)
CBR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measured: Up to 4 weeks
Progression-free Survival (PFS)
PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measured: Up to 4 weeks
Overall survival (OS)
OS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measured: Up to 4 weeks
Duration of response (DOR)
DOR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measured: Up to 4 weeks
Time To Progression (TTP)
TTP as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2018
- Study start15 May 2018
- Primary completion31 Dec 2018 (estimated)
- Study completion31 Dec 2019 (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.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Model description
- Patients received two doses of intravenous ipilimumab (at a dose of 1 mg per kilogram of body weight) every 3 weeks, following by intravenous SHR-1210 (at a fixed dose of 200mg) every 2 weeks.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li Zhang, MD, Sun Yat-sen University
- Investigators
- Li Zhang, MD, Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03527251
- Sponsor's protocol ID
- 2018-FXY-032
- Acronym
- SEQUENCE
- Status last verified
- May 2018
- First submitted
- 28 Apr 2018
- Last updated
- 30 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Evaluating the Safety and Efficacy of CTLA-4 Antibody Ipilimumab Followed by PD-1 Antibody SHR-1210 in Patients With Recurrent or Metastatic Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03527251
- Acronym / sponsor ID
- SEQUENCE / 2018-FXY-032
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- clinical trial, phase I, CTLA-4 antibody, PD-1 antibody, non-small cell lung cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 15 May 2018 (actual)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 17 May 2018 (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.
Immunotherapy has made rapid progress in melanoma, Hodgkin's lymphoma, non-small cell lung cancer, and bladder cancer, etc. Preclinical data suggested that the use of anti-PD-1 antibody in combination with CTLA-4 receptor blockers may increase antitumor activity. The CheckMate-012 study showed that nivolumab and ipilimumab combination therapy achieved an overall response rate of 43% in unselected patients with non-small cell lung cancer, compared with 23% in the nivolumab monotherapy group; and in the PD-L1 positive subgroup, nivolumab in combination with ipilimumab showed a response rate of 57%, while nivolumab alone was 28%. This showed that the combination therapy of nivolumab and ipilimumab can increase the efficacy, but the adverse events of grade 3 or above of combination therapy reach 37%. The toxic side effects limit the widespread use of nivolumab in combination with ipilimumab therapy.
However, since the action of ipilimumab is limited to the initiation of the immune response (antigen presentation and immune cell activation), and its long half-time of 15.4 days, ipilimumab can used as an induction therapy, following by the PD1 monoclonal antibody. This phase I study is aimed to evaluated the safety and efficacy of CTLA-4 antibody followed by PD-1 antibody in patients with recurrent or metastatic non-small cell lung cancer.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients received two doses of intravenous ipilimumab (at a dose of 1 mg per kilogram of body weight) every 3 weeks, following by intravenous SHR-1210 (at a fixed dose of 200mg) every 2 weeks.
| Arm | Type | Receives |
|---|---|---|
| Sequential group | Experimental | Drug: Ipilimumab, Drug: SHR-1210intravenous ipilimumab following by intravenous SHR-1210 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age >=18 years old, male or female;
- Histologically confirmed locally advanced or metastatic non-small-cell lung cancer;
- At least one systemic chemotherapy regimen for locally advanced or metastatic disease (patients received neoadjuvant chemotherapy, concurrent chemoradiotherapy, or adjuvant chemotherapy within 6 months can be considered as first-line system therapy);
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
- At least one measurable lesion according to criteria RECIST v1.1;
Key exclusion criteria (8 listed)
- Driver gene EGFR, ALK and ROS were positive;
- In presence of active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Patients with hormone replacement therapy can be included; Patients with vitiligo or asthma in childhood have been completely relieved, and no intervention in adults can be included; The subjects who needed medical intervention with bronchial dilation were ineligible;
- Patients are using immunity inhibitors or systemic hormone therapy for immunosuppression purpose (such as prednisone > 10 mg/day), except for local hormone therapy.
- Patients were known to be allergic to macromolecular protein, or any components in ipilimumab or SHR-1210;
- Patients with clinical symptoms of central nervous system metastasis (e.g. brain edema, requirement of hormone intervention, or brain metastases progression);
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 |
|---|---|---|
| IpilimumabAlso: YervoyPatients received two doses of intravenous ipilimumab (at a dose of 1 mg per kilogram of body weight) every 3 weeks, following by intravenous SHR-1210 (at a fixed dose of 200mg) every 2 weeks. | Drug | Sequential group |
| SHR-1210Patients received two doses of intravenous ipilimumab (at a dose of 1 mg per kilogram of body weight) every 3 weeks, following by intravenous SHR-1210 (at a fixed dose of 200mg) every 2 weeks. | Drug | Sequential group |
Primary outcome
Safety in the treatment of ipilimumab followed by SHR1210
Time frame: 24 months
Adverse events occurring up to 30 days after the last dose of ipilimumab or SHR1210 are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
6 secondary outcomes
Overall Response Rate (ORR)
Time frame: Up to 4 weeks
Clinical Benefit Response (CBR)
Time frame: Up to 4 weeks
Progression-free Survival (PFS)
Time frame: Up to 4 weeks
Overall survival (OS)
Time frame: Up to 4 weeks
Duration of response (DOR)
Time frame: Up to 4 weeks
Time To Progression (TTP)
Time frame: Up to 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2018.
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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.
Li Zhang, MD principal investigator
Sun Yat-Sen University Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipilimumab and SHR-1210 in people with Non Small Cell Lung Cancer, run by Sun Yat-sen University 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 12 inclusion and 8 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 30 May 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Wenfeng Fang, MD (86-15322302066, fangwf@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety in the treatment of ipilimumab followed by SHR1210 (time frame: 24 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 30 May 2018.