A Phase II Randomized Trial of Neoadjuvant Ivonescimab or Penpulimab Plus Chemotherapy in Resectable NSCLC (NEOINSPIRE)

Yang Fan, MD

Status and phase: Not yet enrolling; Phase 2

Conditions: Immunotherapy; Bispecific Antibody; Neoadjuvant Therapy; AK112; NSCLC

Treatments: Drug: Penpulimab+Chemo; Drug: Ivonescimab+Chemo

Study type: Interventional

Funder types: Other

Identifiers

NCT07086326

AK112-IIT-014

Details and patient eligibility

About

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.

Enrollment: 164 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Voluntarily sign the written Informed Consent Form (ICF) and consent to receive curative surgical treatment.
2. Participants must be aged ≥ 18 years, regardless of gender.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status Score is 0-1.
4. 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).
5. 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.
6. 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.
7. Normal pulmonary function test results.
8. At least one measurable lesion according to RECIST v1.1, amenable to repeated accurate measurements.
9. Adequate cardiac function.
10. Laboratory values obtained during screening or within ≤14 days prior to randomization indicate adequate organ function.
11. For patients planned to receive cisplatin: No hearing impairment.
12. 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.

Exclusion criteria

1. Patients with large cell neuroendocrine carcinoma (LCNEC) or NSCLC mixed with small cell lung cancer components;
2. 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.
3. 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.
4. Any prior systemic or local anti-tumor therapy for NSCLC;
5. Concurrent enrollment in another clinical trial;
6. History of other malignancies (excluding NSCLC) within 3 years prior to randomization;
7. Active autoimmune disease requiring systemic treatment within 2 years prior to randomization;
8. History of major diseases within 1 year prior to randomization;
9. Severe cardiovascular risk factors;
10. 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;
11. Any other conditions deemed unsuitable for enrollment by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

164 participants in 2 patient groups

Ivonescimab+Chemo

Experimental group

Description:

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.

Treatment:

Drug: Ivonescimab+Chemo

Penpulimab+Chemo

Active Comparator group

Description:

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.

Treatment:

Drug: Penpulimab+Chemo