EGFR Positive Non-small Cell Lung CancerPhase 1NCT04001777
A Study of APG-1252 Plus Osimertinib(AZD9291) in EGFR TKI Resistant NSCLC Patients
A Phase 1 study testing APG-1252 and Osimertinib Mesylate Tablets in people with EGFR Positive Non-small Cell Lung Cancer, run by Ascentage Pharma Group Inc. at 4 sites in China.
Trial summary
There are unmet medical needs in patients who resist to EGFR TKIs, especially to osimertinib; APG-1252 shows synergy with osimertinib in both osimertinib treatment naïve and resistant cell lines. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- EGFR Positive Non-small Cell Lung Cancer
- What is being tested?
- APG-1252 and Osimertinib Mesylate Tablets
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 4 sitesChina
- Study dates
- 4 Jul 2019to Jun 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Only applicable to the dose-finding stage:
- Patients with NSCLC with disease progression after first-line EGFR TKI and platinum-based chemotherapy.
- Only applicable to dose-expansion stage:
- Cohort 1: Patients with NSCLC with disease progression after third-generation EGFR TKI and platinum-based chemotherapy.
- Cohort 2: Patients with NSCLC with disease progression after first- or second-generation EGFR TKI and platinum-based chemotherapy.
- Cohort 3: Patients with advanced EGFR-mutated NSCLC not previously treated with TKI.
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- Applicable to any phase:
- Histologically or cytologically confirmed incurable advanced or metastatic non-small cell lung cancer.
- At least 1 measurable lesion (RECIST 1.1).
- Confirmed EGFR mutation positive before start use prior EGFR TKI(s) .
- Willing to biopsy or to supply achieved tumor sample which biopsy after the most recent treatment.
- Male or female patients age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
- Estimated OS ≥3 months.
- Adequate hematologic and bone marrow functions.
- Adequate renal and liver function.
- Brain metastases with clinically controlled neurologic symptoms.
- Had recovered from all toxicities related to prior anticancer therapies to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study.
- Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrhea for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug.
- Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).
- Willingness and ability to comply with study procedures and follow-up examination.
Who cannot join
- Received chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy (hormones for hypothyroidism or estrogen replacement therapy (ERT), anti-estrogen analogs, agonists required to suppress serum testosterone levels are permitted); or any investigational therapy; , or has had tumor embolization or tumor lysis syndrome (TLS) within 28 days prior to the first dose of study drug.
- Received TKIs targeted therapy (except third generation EGFR TKIs) within 14 days prior to the first dose of study drug.
- A history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease.
- Any of the following cardiac criteria: screening period resting period QTC > 470 milliseconds (clinical electrocardiograph report value; if a single time> 470 milliseconds, take the average of 3 inspections); rhythm of resting electrocardiogram (ECG), any clinically important abnormality of conduction or morphology (e.g., complete left bundle branch block, Grade 3 heart block, Grade 2 heart block); family history of congenital long QT prolongation syndrome or long QT syndrome.
- Evidence of any serious or uncontrolled systemic disease; various chronic active infections such as hepatitis B (HBV-DNA ≥ 104 copy number/ml or 2000 IU/ml), hepatitis C and HIV; uncontrollable Hypertensive patients (requires 2 or more drugs to control blood pressure); unstable angina; angina pectoris within 3 months prior to study; congestive heart failure (NYHA class II or higher); myocardial infarction (NSTEMI or STEMI) history in 6 months before study enrollment; severe arrhythmia requiring medical attention; severe liver, kidney, gastrointestinal or metabolic diseases.
- Patients who are unable to stop taking drugs or herbal medicine that are strong inhibitors or inducers of CYP3A within 1 week before the first study drug administration and during the treatment. However, patients who discontinue use of these compounds at least 1 week prior to receiving this regimen are eligible.
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- Hemorrhagic constitution/disease, such as a history of non-chemotherapy-induced thrombocytopenic hemorrhage or a history of ineffective platelet transfusion within 1 year prior to the first dose of study drug; Severe gastrointestinal bleeding occurred within 3 months prior to the first dose of study drug; Active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia (AIHA), etc.
- Use a therapeutic dose of anticoagulant or antiplatelet agent before the first use of APG-1252 or within 7 days of central catheter placement (if platelet count is stable (≧50×109/L), Subjects who previously received aspirin to prevent thrombosis therapy can reuse low-dose aspirin (i.e., up to 100 mg QD) after 3 weeks of study drug treatment; Decisions regarding anticoagulants and antiplatelet therapy will be determined by the investigator and the sponsor; Allow low-dose anticoagulant drugs to maintain central venous catheters open.
- Received a biologic (G-CSF, GM-CSF or erythropoietin) within 28 days prior to the first dose of study drug.
- According to the investigator's judgment, patients who did not fully recover after surgery. Patients who underwent major surgery within 28 days prior to the first study drug and who underwent minor surgery within 7 days prior to the start of the study.
- Other malignancies have been diagnosed within 5 years prior to the first use of the study drug; except effectively treated skin basal cell carcinoma, cutaneous squamous cell carcinoma, and/or effectively resected orthotopic cervical cancer and/or breast cancer.
- Female patients during pregnancy or lactation.
- Previous allergies or intolerance to treatment with osimertinib.
- A diagnosis of febrile neutropenia within one week prior to the first use of the study drug.
- Prior treatment with Bcl-2/Bcl-xL inhibitors.
- Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Trial locations and contacts
4 sites in 1 country.
China4 sites
First Hospital of Jilin University
Changchun, Jilin
Jilin Provincial Cancer Hospital
Changchun, Jilin
Sun-Yat Sen University Cancer Center
Guangzhou, Guangdong, 510060
Henan Provincial people's Hospital
Zhengzhou, Henan
About this study
Official title: A Phase Ib Study of Safety and Efficacy of APG-1252 in Combination With Osimertinib (AZD9291) in EGFR TKI Resistant NSCLC Patients
There are unmet medical needs in patients who resist to EGFR TKIs, especially to osimertinib; APG-1252 shows synergy with osimertinib in both osimertinib treatment naïve and resistant cell lines. This study is to explore the safety and efficacy of the combination of APG-1252 and osimertinib in 3rd generation TKI resistant patients and 3rd generation TKI treatment naïve patients.
Read the detailed description
This is an open-label, single-arm, multicenter, phase 1b study and consists of two stages: dose finding and dose expansion.
The dose-finding stage will explore the safety and tolerability of APG-1252 at different dose levels combined with osimertinib mesylate tablets (hereinafter referred to as osimertinib) at a fixed dose level and determine the MTD and/or RP2D of APG-1252. According to the results from the ongoing phase 1 clinical trials (APG-1252-US-001, APG-1252-AU-001, APG-1252-CH-001) of APG-1252 currently, the starting dose of APG-1252 is set as 240 mg in the study. The 3+3 design will be implemented. The dose for successive cohorts will be escalated to 320 mg and 400 mg or de-escalated to 160 mg and 80 mg based on the safety of the starting dose.
During the dose-expansion period, the efficacy of APG-1252 combined with osimertinib will first be studied in patients with NSCLC that has progressed after treatment with third-generation EGFR TKIs. There will be a total of 20 subjects in Cohort 1. If at least one of the first 10 evaluable patients achieves a response (confirmed complete response [CR] or partial response [PR], assessed by the investigator as per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in the dose-expansion period, Cohort 2 and Cohort 3 will be initiated at the same time.
- Conditions
- EGFR Positive Non-small Cell Lung Cancer
- Being tested
- APG-1252, Osimertinib Mesylate Tablets
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-1252Drug
Also called APG-1252 for injection
Multiple dose cohorts, 30 minute IV infusion, weekly for 3 weeks of a cycle with 21days.
Osimertinib Mesylate TabletsDrug
Also called AZD9291
Osimertinib Mesylate Tablets 40mg/80 mg, one time a day until disease progression
| Study group | Role | What they receive |
|---|---|---|
| APG-1252 plus Osimertinib (AZD9291) | Experimental | APG-1252 will be explored sequentially using a standard 3+3 escalation scheme at the dose escalation phase; Dose of osimertinib will be fixed at 80mg QD based on approved label. Receives: Drug: APG-1252; Drug: Osimertinib Mesylate Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
To determine the maximum tolerated dose (MTD) of APG-1252 in subjects with NSCLC
Measured: 21 days
Recommended Phase 2 dose (RP2D)
Recommended Phase 2 dose (RP2D) of APG-1252 in subjects with NSCLC
Measured: 21 days
Secondary outcomes (1)
efficacy assessment: Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
To assess efficacy in subjects with NSCLC using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Measured: Every 6 weeks up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2019
- Study start4 Jul 2019
- Primary completionDec 2025 (estimated)
- Study completionJun 2026 (estimated)
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 EGFR Positive Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Ascentage Pharma Group Inc.The 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Suzhou Yasheng Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Li Zhang, Professor, Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04001777
- Sponsor's protocol ID
- APG1252NC101
- Status last verified
- Sep 2025
- First submitted
- 20 Jun 2019
- Last updated
- 1 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ma Y, Wu C, Zhao YQ, Cui J, Huang Y, Fang W, Yang Y, Zhao Y, Yang C, Pan W, Xiong D, Men L, Wang H, Yang D, Zhai Y, Zhang L, Zhao H. BCL-2/BCL-xL inhibitor pelcitoclax with osimertinib for EGFR-mutated advanced non-small-cell lung cancer: a phase 1b trial. J Immunother Cancer. 2026 Jul 13;14(7):e014573. doi: 10.1136/jitc-2025-014573.
PubMed 42442920
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study of Safety and Efficacy of APG-1252 in Combination With Osimertinib (AZD9291) in EGFR TKI Resistant NSCLC Patients
- ClinicalTrials.gov ID
- NCT04001777
- Acronym / sponsor ID
- APG1252NC101
- Conditions
- EGFR Positive Non-small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Collaborators
- Suzhou Yasheng Pharmaceutical Co., Ltd.
- Study start
- 4 Jul 2019 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 28 Jun 2019 (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.
There are unmet medical needs in patients who resist to EGFR TKIs, especially to osimertinib; APG-1252 shows synergy with osimertinib in both osimertinib treatment naïve and resistant cell lines. This study is to explore the safety and efficacy of the combination of APG-1252 and osimertinib in 3rd generation TKI resistant patients and 3rd generation TKI treatment naïve patients.
Detailed description
This is an open-label, single-arm, multicenter, phase 1b study and consists of two stages: dose finding and dose expansion.
The dose-finding stage will explore the safety and tolerability of APG-1252 at different dose levels combined with osimertinib mesylate tablets (hereinafter referred to as osimertinib) at a fixed dose level and determine the MTD and/or RP2D of APG-1252. According to the results from the ongoing phase 1 clinical trials (APG-1252-US-001, APG-1252-AU-001, APG-1252-CH-001) of APG-1252 currently, the starting dose of APG-1252 is set as 240 mg in the study. The 3+3 design will be implemented. The dose for successive cohorts will be escalated to 320 mg and 400 mg or de-escalated to 160 mg and 80 mg based on the safety of the starting dose.
During the dose-expansion period, the efficacy of APG-1252 combined with osimertinib will first be studied in patients with NSCLC that has progressed after treatment with third-generation EGFR TKIs. There will be a total of 20 subjects in Cohort 1. If at least one of the first 10 evaluable patients achieves a response (confirmed complete response [CR] or partial response [PR], assessed by the investigator as per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in the dose-expansion period, Cohort 2 and Cohort 3 will be initiated at the same time.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| APG-1252 plus Osimertinib (AZD9291) | Experimental | Drug: APG-1252, Drug: Osimertinib Mesylate TabletsAPG-1252 will be explored sequentially using a standard 3+3 escalation scheme at the dose escalation phase; Dose of osimertinib will be fixed at 80mg QD based on approved label. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients with NSCLC with disease progression after first-line EGFR TKI and platinum-based chemotherapy.
- Cohort 1: Patients with NSCLC with disease progression after third-generation EGFR TKI and platinum-based chemotherapy.
- Cohort 2: Patients with NSCLC with disease progression after first- or second-generation EGFR TKI and platinum-based chemotherapy.
- Cohort 3: Patients with advanced EGFR-mutated NSCLC not previously treated with TKI.
- Histologically or cytologically confirmed incurable advanced or metastatic non-small cell lung cancer.
Key exclusion criteria (16 listed)
- Received chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy (hormones for hypothyroidism or estrogen replacement therapy (ERT), anti-estrogen analogs, agonists required to suppress serum testosterone levels are permitted); or any investigational therapy; , or has had tumor embolization or tumor lysis syndrome (TLS) within 28 days prior to the first dose of study drug.
- Received TKIs targeted therapy (except third generation EGFR TKIs) within 14 days prior to the first dose of study drug.
- A history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease.
- Any of the following cardiac criteria: screening period resting period QTC > 470 milliseconds (clinical electrocardiograph report value; if a single time> 470 milliseconds, take the average of 3 inspections); rhythm of resting electrocardiogram (ECG), any clinically important abnormality of conduction or morphology (e.g., complete left bundle branch block, Grade 3 heart block, Grade 2 heart block); family history of congenital long QT prolongation syndrome or long QT syndrome.
- Evidence of any serious or uncontrolled systemic disease; various chronic active infections such as hepatitis B (HBV-DNA ≥ 104 copy number/ml or 2000 IU/ml), hepatitis C and HIV; uncontrollable Hypertensive patients (requires 2 or more drugs to control blood pressure); unstable angina; angina pectoris within 3 months prior to study; congestive heart failure (NYHA class II or higher); myocardial infarction (NSTEMI or STEMI) history in 6 months before study enrollment; severe arrhythmia requiring medical attention; severe liver, kidney, gastrointestinal or metabolic diseases.
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 |
|---|---|---|
| APG-1252Also: APG-1252 for injectionMultiple dose cohorts, 30 minute IV infusion, weekly for 3 weeks of a cycle with 21days. | Drug | APG-1252 plus Osimertinib (AZD9291) |
| Osimertinib Mesylate TabletsAlso: AZD9291Osimertinib Mesylate Tablets 40mg/80 mg, one time a day until disease progression | Drug | APG-1252 plus Osimertinib (AZD9291) |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 21 days
To determine the maximum tolerated dose (MTD) of APG-1252 in subjects with NSCLC
Recommended Phase 2 dose (RP2D)
Time frame: 21 days
Recommended Phase 2 dose (RP2D) of APG-1252 in subjects with NSCLC
1 secondary outcome
efficacy assessment: Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Time frame: Every 6 weeks up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2025.
- Derived from this study: PubMed 42442920Ma Y, Wu C, Zhao YQ, Cui J, Huang Y, Fang W, Yang Y, Zhao Y, Yang C, Pan W, Xiong D, Men L, Wang H, Yang D, Zhai Y, Zhang L, Zhao H. BCL-2/BCL-xL inhibitor pelcitoclax with osimertinib for EGFR-mutated advanced non-small-cell lung cancer: a phase 1b trial. J Immunother Cancer. 2026 Jul 13;14(7):e014573. doi: 10.1136/jitc-2025-014573.
- 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.
Li Zhang, Professor principal investigator
Sun Yat-Sen University Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APG-1252 and Osimertinib Mesylate Tablets in people with EGFR Positive Non-small Cell Lung Cancer, run by Ascentage Pharma Group Inc. at 4 sites 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 21 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
This study is still under way. Results are not available in the source record yet.
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?
Maximum Tolerated Dose (MTD) (time frame: 21 days). 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 NCT04001777, 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 1 Oct 2025.