NSCLCPhase 2NEOINSPIRENCT07086326
A Phase II Randomized Trial of Neoadjuvant Ivonescimab or Penpulimab Plus Chemotherapy in Resectable NSCLC
A Phase 2 study testing Ivonescimab+Chemo and Penpulimab+Chemo in people with NSCLC and Neoadjuvant Therapy, run by Yang Fan, MD at 5 sites in China.
Trial summary
This is a randomized, open-label, multicenter phase II study. The trial plans to enroll 164 subjects with resectable stage IIA-IIIB (N2) NSCLC. Participants will be randomized 1:1 into either the ivonescimab plus chemotherapy or penpulimab plus chemotherapy treatment arm. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Neoadjuvant Therapy, Immunotherapy
- What is being tested?
- Ivonescimab+Chemo and Penpulimab+Chemo
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 5 sitesChina
- Study dates
- 31 Jul 2025to 30 Dec 2027
- Phase
- Phase 2
- 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
- Voluntarily sign the written Informed Consent Form (ICF) and consent to receive curative surgical treatment.
- Participants must be aged ≥ 18 years, regardless of gender.
- Eastern Cooperative Oncology Group (ECOG) Performance Status Score is 0-1.
- Histologically confirmed resectable Stage IIA-IIIB (N2) non-small cell lung cancer (NSCLC) according to the 9th edition of the TNM staging system for lung cancer by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC).
- Prior to study enrollment, subjects must be evaluated by an attending thoracic surgeon responsible for the surgery to verify eligibility for R0 resection with curative intent.
- NSCLC appears solid or subsolid (not purely ground-glass opacity [GGO]) on CT scan. For subsolid lesions, tumor size (i.e., clinical T stage) should be based solely on the solid component without measuring the GGO portion.
Show all 12Show fewer
- Normal pulmonary function test results.
- At least one measurable lesion according to RECIST v1.1, amenable to repeated accurate measurements.
- Adequate cardiac function.
- Laboratory values obtained during screening or within ≤14 days prior to randomization indicate adequate organ function.
- For patients planned to receive cisplatin: No hearing impairment.
- Women of childbearing potential must have a negative pregnancy test result within 3 days before first treatment; all subjects (male and female) must agree to use appropriate contraceptive methods during the study.
Who cannot join
- Patients with large cell neuroendocrine carcinoma (LCNEC) or NSCLC mixed with small cell lung cancer components;
- Presence of locally advanced unresectable disease (any stage) or metastatic disease (Stage IV). Subjects with contralateral mediastinal lymph node involvement confirmed by PET-CT scan.
- NSCLC diagnosed with EGFR-sensitive mutations or ALK gene translocation. For non-squamous cell carcinoma subjects (including NSCLC with unclear pathology), tumor tissue-based EGFR and ALK testing results must be provided. If EGFR/ALK status is unknown, testing must be performed prior to enrollment. For squamous NSCLC subjects, EGFR/ALK testing is not required during screening if status is unknown.
- Any prior systemic or local anti-tumor therapy for NSCLC;
- Concurrent enrollment in another clinical trial;
- History of other malignancies (excluding NSCLC) within 3 years prior to randomization;
Show all 11Show fewer
- Active autoimmune disease requiring systemic treatment within 2 years prior to randomization;
- History of major diseases within 1 year prior to randomization;
- Severe cardiovascular risk factors;
- History of significant bleeding diathesis or coagulation disorders; clinically significant bleeding symptoms (including but not limited to gastrointestinal hemorrhage, hemoptysis ≥1 teaspoon of fresh blood/clots or pure hemoptysis without sputum, minor blood-tinged sputum allowed; excluding epistaxis and retracted blood-tinged nasal discharge) within 4 weeks prior to randomization;
- Any other conditions deemed unsuitable for enrollment by the investigator.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
China5 sites
Peking University People's Hospital
Beijing, Beijing Municipality, 100000
Hunan Cancer Hospital
Changsha, Hunan
Second Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang
Shanghai Chest Hospital
Shanghai, Shanghai Municipality
The First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi
About this study
Official title: A Prospective, Randomized, Open-label, Controlled Phase Ⅱ Clinical Trial of Ivonescimab Combined With Chemotherapy Versus Penpulimab Combined With Chemotherapy for Neoadjuvant Treatment of Non-small Cell Lung Cancer (NSCLC)
This is a randomized, open-label, multicenter phase II study. The trial plans to enroll 164 subjects with resectable stage IIA-IIIB (N2) NSCLC. Participants will be randomized 1:1 into either the ivonescimab plus chemotherapy or penpulimab plus chemotherapy treatment arm. After 3-4 cycles of neoadjuvant therapy, surgical resection will be performed. The primary objective is to compare the pathological complete response (pCR) rate assessed by local pathologists between ivonescimab-based and penpulimab-based chemo-immunotherapy regimens in the neoadjuvant treatment of resectable NSCLC.
- Conditions
- NSCLC, Neoadjuvant Therapy, Immunotherapy, AK112, Bispecific Antibody
- Being tested
- Ivonescimab+Chemo, Penpulimab+Chemo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab+ChemoDrug
Ivonescimab (AK112) + platinum-based doublet chemotherapy
Penpulimab+ChemoDrug
Penpulimab (AK105) + platinum-based doublet chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Ivonescimab+Chemo | Experimental | Ivonescimab (AK112) + platinum-based doublet chemotherapy as neoadjuvant treatment, administered every 3 weeks (Q3W) for 3-4 cycles. Surgical resection should be performed 4-6 weeks after the last dose, followed by safety follow-up and survival surveillance. Receives: Drug: Ivonescimab+Chemo |
| Penpulimab+Chemo | Active comparator | Penpulimab (AK105) + platinum-based doublet chemotherapy as neoadjuvant treatment, administered every 3 weeks (Q3W) for 3-4 cycles. Surgical resection should be performed 4-6 weeks after the last dose, followed by safety follow-up and survival surveillance. Receives: Drug: Penpulimab+Chemo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response (pCR) Rate
Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by systematic pathological review of surgical specimens.
Measured: Within 1 month after surgery
Secondary outcomes (2)
Major Pathologic Response (MPR) Rate
Major pathologic response (MPR) rate is defined as the percentage of participants with less than 10% of residual viable tumor in lung primary or lymph nodes as evaluated by systematic pathological review of surgical specimens. Viable tumors in situ carcinoma should not be included in MPR calculation.
Measured: Within 1 month after surgery
Event-Free Survival (EFS)
Defined as the time from the first dose to the occurrence of any of the following events (whichever occurs first), assessed in the Intention-To-Treat (ITT) population: Disease progression (based on RECIST v1.1 criteria by investigators); Local recurrence or distant metastasis; Death from any cause
Measured: the time from the first dose to the occurrence of any of the following events (whichever occurs first), assessed in the Intention-To-Treat (ITT) population: Disease progression (based on RECIST v1.1 criteria by investigators); Local recurrence or dist
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2025
- Study start31 Jul 2025 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yang Fan, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Yang Fan, MD, Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07086326
- Sponsor's protocol ID
- AK112-IIT-014
- Acronym
- NEOINSPIRE
- Status last verified
- Jul 2025
- First submitted
- 17 Jul 2025
- Last updated
- 25 Jul 2025
- 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 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Open-label, Controlled Phase Ⅱ Clinical Trial of Ivonescimab Combined With Chemotherapy Versus Penpulimab Combined With Chemotherapy for Neoadjuvant Treatment of Non-small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT07086326
- Acronym / sponsor ID
- NEOINSPIRE / AK112-IIT-014
- Conditions
- NSCLC, Neoadjuvant Therapy, Immunotherapy, AK112, Bispecific Antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 164 participants (estimated)
- Lead sponsor
- Yang Fan, MDUniversity, hospital or other
- Study start
- 31 Jul 2025 (estimated)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 25 Jul 2025 (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 is a randomized, open-label, multicenter phase II study. The trial plans to enroll 164 subjects with resectable stage IIA-IIIB (N2) NSCLC. Participants will be randomized 1:1 into either the ivonescimab plus chemotherapy or penpulimab plus chemotherapy treatment arm. After 3-4 cycles of neoadjuvant therapy, surgical resection will be performed. The primary objective is to compare the pathological complete response (pCR) rate assessed by local pathologists between ivonescimab-based and penpulimab-based chemo-immunotherapy regimens in the neoadjuvant treatment of resectable NSCLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ivonescimab+Chemo | Experimental | Drug: Ivonescimab+ChemoIvonescimab (AK112) + platinum-based doublet chemotherapy as neoadjuvant treatment, administered every 3 weeks (Q3W) for 3-4 cycles. Surgical resection should be performed 4-6 weeks after the last dose, followed by safety follow-up and survival surveillance. |
| Penpulimab+Chemo | Active comparator | Drug: Penpulimab+ChemoPenpulimab (AK105) + platinum-based doublet chemotherapy as neoadjuvant treatment, administered every 3 weeks (Q3W) for 3-4 cycles. Surgical resection should be performed 4-6 weeks after the last dose, followed by safety follow-up and survival surveillance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Voluntarily sign the written Informed Consent Form (ICF) and consent to receive curative surgical treatment.
- Participants must be aged ≥ 18 years, regardless of gender.
- Eastern Cooperative Oncology Group (ECOG) Performance Status Score is 0-1.
- Histologically confirmed resectable Stage IIA-IIIB (N2) non-small cell lung cancer (NSCLC) according to the 9th edition of the TNM staging system for lung cancer by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC).
- Prior to study enrollment, subjects must be evaluated by an attending thoracic surgeon responsible for the surgery to verify eligibility for R0 resection with curative intent.
Key exclusion criteria (11 listed)
- Patients with large cell neuroendocrine carcinoma (LCNEC) or NSCLC mixed with small cell lung cancer components;
- Presence of locally advanced unresectable disease (any stage) or metastatic disease (Stage IV). Subjects with contralateral mediastinal lymph node involvement confirmed by PET-CT scan.
- NSCLC diagnosed with EGFR-sensitive mutations or ALK gene translocation. For non-squamous cell carcinoma subjects (including NSCLC with unclear pathology), tumor tissue-based EGFR and ALK testing results must be provided. If EGFR/ALK status is unknown, testing must be performed prior to enrollment. For squamous NSCLC subjects, EGFR/ALK testing is not required during screening if status is unknown.
- Any prior systemic or local anti-tumor therapy for NSCLC;
- Concurrent enrollment in another clinical trial;
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 |
|---|---|---|
| Ivonescimab+ChemoIvonescimab (AK112) + platinum-based doublet chemotherapy | Drug | Ivonescimab+Chemo |
| Penpulimab+ChemoPenpulimab (AK105) + platinum-based doublet chemotherapy | Drug | Penpulimab+Chemo |
Primary outcome
Pathologic Complete Response (pCR) Rate
Time frame: Within 1 month after surgery
Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by systematic pathological review of surgical specimens.
2 secondary outcomes
Major Pathologic Response (MPR) Rate
Time frame: Within 1 month after surgery
Event-Free Survival (EFS)
Time frame: the time from the first dose to the occurrence of any of the following events (whichever occurs first), assessed in the Intention-To-Treat (ITT) population: Disease progression (based on RECIST v1.1 criteria by investigators); Local recurrence or dist
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 25 Jul 2025.
- Individual participant dataSharing planned: No
Related trials for NSCLC
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivonescimab+Chemo and Penpulimab+Chemo in people with NSCLC and Neoadjuvant Therapy, run by Yang Fan, MD at 5 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 12 inclusion and 11 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: opening soon, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 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?
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?
Pathologic Complete Response (pCR) Rate (time frame: Within 1 month after surgery). 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 25 Jul 2025.