Phase II Multicenter Study of Neoadjuvant Sacituzumab Govitecan and Zimberelimab in Resectable Non-Small Cell Lung Cancer
- Trial ID
- 2024-517561-16-00
- Protocol
- AIO-TRK/YMO-0224
- Sponsor
- AIO-Studien gGmbH
Trial statistics
Objectives
The primary objective is to evaluate the effect of neoadjuvant sacituzumab govitecan plus zimberelimab on the pathological complete response rate in patients with resectable non-small cell lung cancer. Secondary objectives include:
- Assessment of the major pathological response rate in the resected primary tumor and all resected lymph nodes.
- Evaluation of the objective response rate following completion of neoadjuvant therapy using RECIST 1.1.
- Assessment of the nodal downstaging rate, defined as the reduction from clinical nodal positive to pathologic nodal negative via histopathological analysis.
- Determination of the time to surgery from the final dose of neoadjuvant treatment.
- Evaluation of the surgical resection rate.
- Assessment of disease-free survival and overall survival.
- Evaluation of safety and quality of life.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of adults aged 18 to 64 years diagnosed with resectable non-small cell lung cancer. Eligible individuals must present with stage II to IIIB (N2) disease according to UICC8 guidelines and demonstrate a pathological complete response rate following neoadjuvant therapy. Participants are required to have an ECOG performance status of 0-1 and adequate hematologic counts, including specific levels for hemoglobin, absolute neutrophil count, and platelets. Additional requirements include stable liver function and a creatinine clearance of at least 30 mL/min. Both male and female subjects are included, with specific contraceptive requirements for women of childbearing potential.
Plans and Procedures
This multicenter, therapeutic explorative phase II study evaluates the efficacy of neoadjuvant sacituzumab govitecan combined with zimberelimab, followed by adjuvant therapy consisting of zimberelimab with or without sacituzumab govitecan. The primary objective is to determine the pathological complete response rate in patients with resectable non-small cell lung cancer. The study design involves an initial screening period to confirm eligibility based on histological confirmation of stage II to IIIB disease, specific hematologic, hepatic, and renal function requirements, and ECOG performance status. Following the neoadjuvant phase, participants undergo surgical resection, followed by the adjuvant treatment phase. Secondary endpoints include major pathological response, objective response rate, disease-free survival, and overall survival. The trial is estimated to continue until June 30, 2031.
Treatment
Zimberelimab is administered as a concentrate for solution for infusion. The dosage is 360 mg, provided via intravenous infusion.
Sacituzumab govitecan, formulated as Trodelvy 200 mg powder for concentrate for solution for infusion, is administered as a solution for infusion. The dosage is 10 mg/kg via intravenous infusion.
Efficacy
The primary efficacy endpoint is the pathological complete response (pCR) rate. This is defined as the proportion of patients whose resected primary tumor and all resected lymph nodes are negative for residual viable tumor cells.
Secondary endpoints include:
- Major pathological response (MPR) rate in the resected primary tumor and all resected lymph nodes, defined as the proportion of resected samples showing 10% or less residual viable tumor cells.
- Objective response rate (ORR) following completion of neoadjuvant therapy, as assessed via imaging using RECIST 1.1.
- Surgical resection rate and time to surgery following C4D1.
- Disease-free survival (DFS), measured from inclusion to any recurrence of non-small cell lung cancer or death from any cause in the intent-to-treat population.
- Overall survival (OS), measured from inclusion to death from any cause in the intent-to-treat population.
- Adverse events (AE) assessed using CTCAE 5.
- Quality of life (QoL) evaluated using the EORTC-QLQ-C30 and EQ-5D-5L instruments.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients ≥ 18 years of age at the time of informed consent signature.
- Histological confirmed, resectable NSCLC, stage II to IIIB (N2) (UICC8), after completion of the full staging according to current guidelines including systematic mediastinal staging by EBUS and/or surgery, PD-L1 testing of tumor tissue, PET-CT, and cMRI.
- Adequate hematologic counts without growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets ≥ 100,000/μL).
- Adequate liver function (bilirubin ≤ 1.5 ULN, AST and ALT ≤ 2.5 x ULN)
- Creatinine clearance ≥ 30 mL/min as assessed by the CKD-EPI method.
- Patients are amenable to neoadjuvant treatment followed by surgery and adjuvant treatment.
- ECOG 0-1
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
- Female subjects of childbearing potential (WOCBP) must use highly effective contraceptive measures during the study and for 6 months after the last dose of study drug and must not be breast-feeding prior to start of trial. Non-child-bearing potential must be evidenced by fulfilling one of the following criteria at screening: a. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments b. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution. c. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Exclusion Criteria
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
- Has previously received topoisomerase 1 inhibitors.
- Has an active second malignancy. Note: Patients with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll.
- Has an active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease), or has a history of GI perforation within 6 months prior to enrollment.
- Has an active serious infection requiring systemic therapy, or has a history of an active serious infection that required systemic therapy within 7 days prior to enrollment.
- Female subjects who are pregnant or breast-feeding or patients of reproductive potential who are not employing a highly effective method of birth control (failure rate of less than 1% per year).
- Medication that is known to interfere with any of the agents applied in the trial.
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- Has received prior radiotherapy of the primary tumor and/or mediastinum.
- Must have recovered to grade ≤ 1 from all AEs due to previous therapies for other medical conditions. Patients participating in observational studies are eligible. Must have recovered from any previous surgical procedure prior to enrollment
- Has previously received topoisomerase 1 inhibitors
- Has an active second malignancy. Note: Patients with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll.
- Has an active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease), or has a history of GI perforation within 6 months prior to enrollment.
- Has an active serious infection requiring systemic therapy, or has a history of an active serious infection that required systemic therapy within 7 days prior to enrollment.
- Female subjects who are pregnant or breast-feeding or patients of reproductive potential who are not employing a highly effective method of birth control (failure rate of less than 1% per year).
- Medication that is known to interfere with any of the agents applied in the trial.
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
- Any condition or disease, which might interfere with the subject's ability to comply with the study procedures (e.g. dementia).
- Has been incarcerated or involuntarily institutionalized by court order or by the authorities.
- Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 30 Jun 2025 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Zimberelimab | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 360 | 54 | PRD9450049 |
Trodelvy 200 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 10 | 30 | PRD9351384 |