SCLC, Extensive StagePhase 1NCT05116007
Anti-PD-1 and VEGF Bispecific Antibody AK112 in Combination With Chemotherapy in Patients With ES-SCLC
A Phase 1 study testing AK112, Etoposide and Carboplatin in people with SCLC, Extensive Stage, run by Akeso at 1 site in China.
Trial summary
Phase Ib open label, multicenter study to evaluate the efficacy and safety of anti-PD-1 and VEGF bispecific antibody (AK112) combined with chemotherapy in patients with ES-SCLC. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- SCLC, Extensive Stage
- What is being tested?
- AK112, Etoposide and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 29 Mar 2021to 4 Dec 2023
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 to 75 years old (at the time of inform consent obtained).
- Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
- Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system).
- Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue obtained from either a core or excisional tumor biopsy.
- Have a life expectancy of at least 3 months.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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- Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator
- Has adequate organ function
- All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
Who cannot join
- Undergone major surgery within 30 days prior to the first dose of study treatment
- History of prior malignancy except that basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Active central nervous system (CNS) metastases
- History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e.,corticosteroids or immunosuppressive drugs).
- Active infection requiring systemic therapy
- Active Hepatitis B or Hepatitis C
- History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment;
- Pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib Clinical Study of Anti-PD-1 and VEGF Bispecific Antibody AK112 in Combination With Etoposide and Carboplatin for the First-line Treatment of Patients With Extensive Stage Small Cell Lung Cancer
Phase Ib open label, multicenter study to evaluate the efficacy and safety of anti-PD-1 and VEGF bispecific antibody (AK112) combined with chemotherapy in patients with ES-SCLC.
Read the detailed description
Small cell lung cancer (SCLC) is an aggressive type of neuroendocrine tumor with the majority of patients (about 60-70%) being diagnosed with metastatic disease and with a median survival ranging from 7 to 12 months. Combination chemotherapy , namely a platinum and etoposide-based regimen, represents the cornerstone of treatment for extensive stage SCLC(ES-SCLC). Despite this the duration of response is short and nearly all patients develop disease relapse or progression. The recent approval of atezolizumab in combination with carboplatin and etoposide as first line in patients with ES- SCLC is surely a step forward in the understanding the molecular landscape and treatment of this complex tumor, but new therapeutic approaches need to be explored.This trial aims to assess the safety and efficacy of a new therapeutic strategy that combines to carboplatin and etoposide, and a new drug AK112.The treatment will start with an induction phase during which eligible patients will receive, by intravenous way, a combination of the above mentioned drugs according to a specific administration regimen. This phase will last about 12 weeks. Thereafter the treatment will proceed with a maintenence phase lasting for a maximum of 24 months during which the patients will receive only AK112, by intravenous way. Treatment will be discontnued in case of until the toxicity became intolerable, the investigator determined that there was no further clinical benefit (based on a combination of RECIST V1.1 imaging assessment and clinical status), 24 months of treatment was completed, or the study was withdrawn for other reasons. During the study period the patients will undergo to periodic visits and laboratory, radiologic assessments to monitor the efficacy and the safety of the ongoing treatment.
- Conditions
- SCLC, Extensive Stage
- Being tested
- AK112, Etoposide, Carboplatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK112Drug
IV infusion
EtoposideDrug
Etoposide intravenous infusion was administered at a dose of 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).
CarboplatinDrug
Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4)
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Subjects receive AK112 plus Etoposide and Carboplatin every 3- week cycle (Q3W) for 4 cycles followed by AK112 until progression. Receives: Drug: AK112; Drug: Etoposide; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Grade 3 or higher adverse events (AEs)
Frequency and severity of adverse events measured according to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 5.0
Measured: Interval between the date of enrollment and the date of death from any cause, up to a maximum of 2 years
Objective Response Rate (ORR)
ORR is proportion of subjects with complete response(CR) or partial response(PR). Tumor responses will be evaluated according to RECIST 1.1 criteria. Patients with no tumor assessment after baseline will be classified as non-responders.
Measured: Interval between the date of enrollment and the date of death from any cause, up to a maximum of 18 months.
Secondary outcomes (3)
Disease control rate (DCR)
DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST V1.1
Measured: Interval between the date of enrollment and the date of death due to any cause , up to a maximum of approximately 2 years
Progression free survival (PFS)
PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1) assessed by the investigator or death due to any cause (whichever occurs first)
Measured: Interval between the date of enrollment and the date of progressive disease, or death due to any cause (whichever occurs first), up to a maximum of 24 months.
Overall survival (OS)
OS is the time from the date of randomization or first dosing date to death due to any cause.
Measured: Interval between the date of enrollment and the date of death from any cause, up to a maximum of 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2021
- Study start29 Mar 2021
- Primary completion4 Dec 2023
- Study completion4 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SCLC, Extensive StageStudies of the same condition, open and under way.
- More trials run by AkesoThe 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akeso
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shun Lu, Professor, Principal investigator, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, P. R. China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05116007
- Sponsor's protocol ID
- AK112-103
- Status last verified
- May 2024
- First submitted
- 21 Sep 2021
- Last updated
- 31 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chen Z, Wu L, Wang Q, Yu Y, Liu X, Ma R, Li T, Li Y, Song X, Li L, Zhao W, Wang Q, Xu X, Lu S. Brief Report: Ivonescimab Combined With Etoposide Plus Carboplatin as First-Line Treatment for Extensive-Stage SCLC: Results of a Phase 1b Clinical Trial. J Thorac Oncol. 2025 Feb;20(2):233-239. doi: 10.1016/j.jtho.2024.10.013. Epub 2024 Oct 28.
PubMed 39490738
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Clinical Study of Anti-PD-1 and VEGF Bispecific Antibody AK112 in Combination With Etoposide and Carboplatin for the First-line Treatment of Patients With Extensive Stage Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05116007
- Acronym / sponsor ID
- AK112-103
- Conditions
- SCLC, Extensive Stage
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- AkesoIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2021 (actual)
- Primary completion
- 4 Dec 2023 (actual)
- Study completion
- 4 Dec 2023 (actual)
- First posted
- 10 Nov 2021 (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.
Phase Ib open label, multicenter study to evaluate the efficacy and safety of anti-PD-1 and VEGF bispecific antibody (AK112) combined with chemotherapy in patients with ES-SCLC.
Detailed description
Small cell lung cancer (SCLC) is an aggressive type of neuroendocrine tumor with the majority of patients (about 60-70%) being diagnosed with metastatic disease and with a median survival ranging from 7 to 12 months. Combination chemotherapy , namely a platinum and etoposide-based regimen, represents the cornerstone of treatment for extensive stage SCLC(ES-SCLC). Despite this the duration of response is short and nearly all patients develop disease relapse or progression. The recent approval of atezolizumab in combination with carboplatin and etoposide as first line in patients with ES- SCLC is surely a step forward in the understanding the molecular landscape and treatment of this complex tumor, but new therapeutic approaches need to be explored.This trial aims to assess the safety and efficacy of a new therapeutic strategy that combines to carboplatin and etoposide, and a new drug AK112.The treatment will start with an induction phase during which eligible patients will receive, by intravenous way, a combination of the above mentioned drugs according to a specific administration regimen. This phase will last about 12 weeks. Thereafter the treatment will proceed with a maintenence phase lasting for a maximum of 24 months during which the patients will receive only AK112, by intravenous way. Treatment will be discontnued in case of until the toxicity became intolerable, the investigator determined that there was no further clinical benefit (based on a combination of RECIST V1.1 imaging assessment and clinical status), 24 months of treatment was completed, or the study was withdrawn for other reasons. During the study period the patients will undergo to periodic visits and laboratory, radiologic assessments to monitor the efficacy and the safety of the ongoing treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: AK112, Drug: Etoposide, Drug: CarboplatinSubjects receive AK112 plus Etoposide and Carboplatin every 3- week cycle (Q3W) for 4 cycles followed by AK112 until progression. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 18 to 75 years old (at the time of inform consent obtained).
- Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
- Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system).
- Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue obtained from either a core or excisional tumor biopsy.
- Have a life expectancy of at least 3 months.
Key exclusion criteria (8 listed)
- Undergone major surgery within 30 days prior to the first dose of study treatment
- History of prior malignancy except that basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Active central nervous system (CNS) metastases
- History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e.,corticosteroids or immunosuppressive drugs).
- Active infection requiring systemic therapy
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 |
|---|---|---|
| AK112IV infusion | Drug | Experimental |
| EtoposideEtoposide intravenous infusion was administered at a dose of 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4). | Drug | Experimental |
| CarboplatinCarboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4) | Drug | Experimental |
Primary outcome
Incidence of Grade 3 or higher adverse events (AEs)
Time frame: Interval between the date of enrollment and the date of death from any cause, up to a maximum of 2 years
Frequency and severity of adverse events measured according to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 5.0
Objective Response Rate (ORR)
Time frame: Interval between the date of enrollment and the date of death from any cause, up to a maximum of 18 months.
ORR is proportion of subjects with complete response(CR) or partial response(PR). Tumor responses will be evaluated according to RECIST 1.1 criteria. Patients with no tumor assessment after baseline will be classified as non-responders.
3 secondary outcomes
Disease control rate (DCR)
Time frame: Interval between the date of enrollment and the date of death due to any cause , up to a maximum of approximately 2 years
Progression free survival (PFS)
Time frame: Interval between the date of enrollment and the date of progressive disease, or death due to any cause (whichever occurs first), up to a maximum of 24 months.
Overall survival (OS)
Time frame: Interval between the date of enrollment and the date of death from any cause, up to a maximum of 24 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2024.
- Derived from this study: PubMed 39490738Chen Z, Wu L, Wang Q, Yu Y, Liu X, Ma R, Li T, Li Y, Song X, Li L, Zhao W, Wang Q, Xu X, Lu S. Brief Report: Ivonescimab Combined With Etoposide Plus Carboplatin as First-Line Treatment for Extensive-Stage SCLC: Results of a Phase 1b Clinical Trial. J Thorac Oncol. 2025 Feb;20(2):233-239. doi: 10.1016/j.jtho.2024.10.013. Epub 2024 Oct 28.
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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.
Shun Lu, Professor principal investigator
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, P. R. China
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 AK112, Etoposide and Carboplatin in people with SCLC, Extensive Stage, run by Akeso 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 9 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: finished, as of the sponsor's last update on 31 May 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Grade 3 or higher adverse events (AEs) (time frame: Interval between the date of enrollment and the date of death from any cause, up to a maximum of 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05116007, which also lists 1 linked publication.
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 31 May 2024.