Non-Small-Cell Lung CancerPhase 3KANNON-2NCT06281964
Efficacy and Safety Evaluation of PLB1004 in Patients With Non-squamous NSCLC Harboring EGFR Exon 20 Insertion.
A Phase 3 study testing PLB1004 and Pemetrexed+（carboplatin or Cisplatin）with or without Sintilimab in people with Non-Small-Cell Lung Cancer, run by Avistone Biotechnology Co., Ltd. at 1 site in China.
Trial summary
Efficacy and safety evaluation of PLB1004 in patients with locally advanced/metastatic non-squamous NSCLCharboring EGFR exon 20 insertion. 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?
- PLB1004 and Pemetrexed+（carboplatin or Cisplatin）with or without Sintilimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 327 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2023to 30 Jun 2030
- Phase
- Phase 3
- 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
- Ability to understand and willingness to sign a written informed consent document.
- Aged at least 18 years old.
- Histologically or cytologically confirmed locally advanced or metastatic NSCLC (stage IIIB~IV).
- Tumor tissue is positive for EGFR Ex20ins as documentally confirmed by next-generation sequencing (NGS) testing or written confirmation of PCR testing by a local laboratory accredited by the Clinical Laboratory Improvement Act Amendments (CLIA), International Organization for Standardization/Independent Ethics Committee (ISO/IEC), American College of Pathologists (CAP), or a central laboratory designated by the sponsor by a tertiary A hospital or with Clinical Laboratory Improvement Act Amendments (CLIA), International Organization for Standardization/Independent Ethics Committee (ISO/IEC), American College of Pathologists (CAP) accreditation (or other equivalent accreditation).
- At least one measurable lesion as defined by RECISTV1.1（Brain lesions were not included in measurable target lesions）
- ECOG performance status 0 to 1.
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- Life expectancy is not less than 12 weeks.
- No previous systemic treatment for locally advanced or metastatic non-squamous cell cancer NSCLC. Note: Subjects are allowed to receive neoadjuvant/adjuvant therapy as long as the relevant therapy has ended at least 6 months before the disease is diagnosed as locally progressive or metastatic tumors
- -
Who cannot join
- Have one of the following previous anti-tumor treatments: prior to the first dose of PLB1004
- Any anti-EGFR TKI for the EGFR ex20ins mutation.. b) Received Chinese patent drugs with anti-tumor indications within 1 week before administration of the first study drugReceived Chinese patent drugs with anti-tumor indications within 1 week before administration of the first study drug c) required administration of the multidrug and toxin efflux protein (MATE) transporter substrate metformin within 1 week before and during the first study drug administration d）Strong inhibitors or strong inducers of the cytochrome P450 3A4 enzyme (CYP3A4) were required within 1 week before and during the study e) required immunosuppressive medication within 2 weeks before or during the first dose of study drug f) Major surgery within 4 weeks prior to starting PLB1004 or who have not recovered from side effects of such procedure except for the biopsy of Thoracoscopy and the clinical test of Mediastinoscopy could ≤ 7 days prior to starting PLB1004 g) Radiotherapy to lung fields and whole-brain fields ≤4 weeks prior to starting PLB1004. For all other anatomic sites, radiotherapy ≤2 weeks prior to starting PLB1004 or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions is not included.
- Patients with spinal cord compression ,brain membrane metastasis and symptomatic central nervous system (CNS), who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study manage CNS symptoms.
- Before randomization, patients did not recover from any toxicity and/or complications of previous chemotherapy, surgery, radiotherapy and other anti-cancer treatments, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for hair loss and irrecoverable permanent radiation damage
- Did not recover from any toxicity and/or complications of previous anti-cancer treatments such as chemotherapy, surgery, and radiotherapy, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for alopecia and irrecoverable permanent radiation damage
- A tendency to coagulopathy or bleeding, including an arterial or venous thromboembolic event (including a history of myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other major thromboembolism) within 6 months before randomization; Any life-threatening bleeding event (including the need for blood transfusion, surgical or local treatment, or continued medical therapy) or major vascular invasion was considered by the investigator to be bleeding prone
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- Severe cardiac disease, such as any serious arrhythmia (including ventricular arrhythmia, drug-refractory supraventricular and other arrhythmias), grade III or higher cardiac dysfunction (New York Heart Association [NYHA], see Appendix 4 for details), and left ventricular ejection fraction (LVEF) <50% on echocardiography;
- Mean corrected QT intervals (QTcF) of three electrocardiograms during screening, calculated according to Fridericia's formula at rest, were >470 ms;
- Presence of uncontrolled hypertension (treated systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg)
- Dysphagia, or active digestive disease or major gastrointestinal surgery that may affect the administration or absorption of the study drug (e.g., ulcerative lesions, uncontrolled nausea, vomiting, diarrhea, and malabsorption syndromes);
- Allergy or intolerance to the drug class and excipient components of the study drug
- pregnant or nursing women.
- Received live vaccine within 4 weeks before randomization;
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Randomized, Controlled, Open Label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of PLB1004 Versus Platinum-based Chemotherapy With or Without Sintilimab of Advanced NSCLC With EGFR Exon 20 Ins Mutations
Efficacy and safety evaluation of PLB1004 in patients with locally advanced/metastatic non-squamous NSCLCharboring EGFR exon 20 insertion.
Read the detailed description
Randomized, controlled, open label, multicenter phase III study to evaluate the efficacy and safety of PLB1004 Versus platinum-based chemotherapy with or without Sintilimab in the first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) Exon 20 insertion(ex 20) mutations.
- Conditions
- Non-Small-Cell Lung Cancer
- Being tested
- PLB1004, Pemetrexed+（carboplatin or Cisplatin）with or without Sintilimab
- Keywords
- Non-Small-Cell Lung Cancer, EGFR, NSCLC, Lung Cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PLB1004Drug
Participants received oral PLB1004 240mg on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive oral PLB1004 240mg and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
Pemetrexed+（carboplatin or Cisplatin）with or without SintilimabDrug
Participants received IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Sintilimab 200mg intravenously administered on day 1 q3w per investigator's decision. Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive oral PLB1004 and 500 mg/m^2 of pemetrexed on Day 1 q3w and Sintilimab 200mg intravenously administered on day 1 q3w per investigator's decision. until disease progression in the maintenance period.
| Study group | Role | What they receive |
|---|---|---|
| PLB1004 | Experimental | PLB1004 given alone as monotherapy Receives: Drug: PLB1004 |
| platinum-based chemotherapy with or without Sintilimab | Active comparator | platinum-based chemotherapy with or without Sintilimab Receives: Drug: Pemetrexed+（carboplatin or Cisplatin）with or without Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) by BICR
Progression-free survival (PFS) as assessed by a Blind Independent Center Review Committee (BICR) with reference to RECIST v1.1 for Solid tumors
Measured: 3 years
Secondary outcomes (7)
Progression-Free Survival (PFS) by the investigator
Refer to RECIST v1.1, PFS assessed by the investigator
Measured: 2 years
Intracranial Overall Response Rate（ORR）
To evaluate the intracranial Overall Response Rate（ORR）which is defined by investigator as the proportion of subjects with Intracranial disease confirmed best overall response of complete response or partial response per RECIST v 1.1.
Measured: 3 years
Duration of Response (DOR)
DOR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first.
Measured: 3 years
Disease Control Rate (DCR)
DCR is defined as the percentage of participants achieving complete or partial response or stable disease as defined per RECIST v 1.1
Measured: 3 years
Overall Survival (OS)
OS is defined as the time from the date of the first dose until the date of death due to any cause.
Measured: 3 years
Incidence of Treatment-Emergent Adverse Events (TEAEs)
A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug assessed by CTCAE v5.0
Measured: 3 years
Plasma concentrations of PLB1004 and metabolites may be combined with data from other clinical studies
Plasma concentrations of PLB1004 and metabolites may be combined with data from other clinical studies
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study start1 Dec 2023
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2030 (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 Avistone Biotechnology Co., Ltd.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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 327 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Avistone Biotechnology Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06281964
- Sponsor's protocol ID
- PLB1004-III-01
- Acronym
- KANNON-2
- Status last verified
- Dec 2025
- First submitted
- 31 Jan 2024
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Controlled, Open Label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of PLB1004 Versus Platinum-based Chemotherapy With or Without Sintilimab of Advanced NSCLC With EGFR Exon 20 Ins Mutations
- ClinicalTrials.gov ID
- NCT06281964
- Acronym / sponsor ID
- KANNON-2 / PLB1004-III-01
- Conditions
- Non-Small-Cell Lung Cancer
- Keywords
- Non-Small-Cell Lung Cancer, EGFR, NSCLC, Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 327 participants (estimated)
- Lead sponsor
- Avistone Biotechnology Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Dec 2023 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 28 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.
Efficacy and safety evaluation of PLB1004 in patients with locally advanced/metastatic non-squamous NSCLCharboring EGFR exon 20 insertion.
Detailed description
Randomized, controlled, open label, multicenter phase III study to evaluate the efficacy and safety of PLB1004 Versus platinum-based chemotherapy with or without Sintilimab in the first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) Exon 20 insertion(ex 20) mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PLB1004 | Experimental | Drug: PLB1004PLB1004 given alone as monotherapy |
| platinum-based chemotherapy with or without Sintilimab | Active comparator | Drug: Pemetrexed+（carboplatin or Cisplatin）with or without Sintilimabplatinum-based chemotherapy with or without Sintilimab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Ability to understand and willingness to sign a written informed consent document.
- Aged at least 18 years old.
- Histologically or cytologically confirmed locally advanced or metastatic NSCLC (stage IIIB~IV).
- Tumor tissue is positive for EGFR Ex20ins as documentally confirmed by next-generation sequencing (NGS) testing or written confirmation of PCR testing by a local laboratory accredited by the Clinical Laboratory Improvement Act Amendments (CLIA), International Organization for Standardization/Independent Ethics Committee (ISO/IEC), American College of Pathologists (CAP), or a central laboratory designated by the sponsor by a tertiary A hospital or with Clinical Laboratory Improvement Act Amendments (CLIA), International Organization for Standardization/Independent Ethics Committee (ISO/IEC), American College of Pathologists (CAP) accreditation (or other equivalent accreditation).
- At least one measurable lesion as defined by RECISTV1.1（Brain lesions were not included in measurable target lesions）
Key exclusion criteria (14 listed)
- Have one of the following previous anti-tumor treatments: prior to the first dose of PLB1004
- Patients with spinal cord compression ,brain membrane metastasis and symptomatic central nervous system (CNS), who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study manage CNS symptoms.
- Before randomization, patients did not recover from any toxicity and/or complications of previous chemotherapy, surgery, radiotherapy and other anti-cancer treatments, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for hair loss and irrecoverable permanent radiation damage
- Did not recover from any toxicity and/or complications of previous anti-cancer treatments such as chemotherapy, surgery, and radiotherapy, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for alopecia and irrecoverable permanent radiation damage
- A tendency to coagulopathy or bleeding, including an arterial or venous thromboembolic event (including a history of myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other major thromboembolism) within 6 months before randomization; Any life-threatening bleeding event (including the need for blood transfusion, surgical or local treatment, or continued medical therapy) or major vascular invasion was considered by the investigator to be bleeding prone
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 |
|---|---|---|
| PLB1004Participants received oral PLB1004 240mg on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive oral PLB1004 240mg and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period. | Drug | PLB1004 |
| Pemetrexed+（carboplatin or Cisplatin）with or without SintilimabParticipants received IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Sintilimab 200mg intravenously administered on day 1 q3w per investigator's decision. Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive oral PLB1004 and 500 mg/m^2 of pemetrexed on Day 1 q3w and Sintilimab 200mg intravenously administered on day 1 q3w per investigator's decision. until disease progression in the maintenance period. | Drug | platinum-based chemotherapy with or without Sintilimab |
Primary outcome
Progression-Free Survival (PFS) by BICR
Time frame: 3 years
Progression-free survival (PFS) as assessed by a Blind Independent Center Review Committee (BICR) with reference to RECIST v1.1 for Solid tumors
7 secondary outcomes
Progression-Free Survival (PFS) by the investigator
Time frame: 2 years
Intracranial Overall Response Rate（ORR）
Time frame: 3 years
Duration of Response (DOR)
Time frame: 3 years
Disease Control Rate (DCR)
Time frame: 3 years
Overall Survival (OS)
Time frame: 3 years
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: 3 years
Plasma concentrations of PLB1004 and metabolites may be combined with data from other clinical studies
Time frame: 3 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 23 Apr 2026.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PLB1004 and Pemetrexed+（carboplatin or Cisplatin）with or without Sintilimab in people with Non-Small-Cell Lung Cancer, run by Avistone Biotechnology Co., Ltd. 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 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: enrolling by invitation, as of the sponsor's last update on 23 Apr 2026. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Progression-Free Survival (PFS) by BICR (time frame: 3 years). 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 23 Apr 2026.