A multicenter phase II study of neoadjuvant sacituzumab govitecan plus zimberelimab followed by adjuvant zimberelimab with or without sacituzumab govitecan in patients with resectable non-small cell lung cancer (NeoTRACE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AIO-Studien gGmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-09-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the effect of neoadjuvant Sacituzumab govitecan (SG) plus Zimberelimab (ZIM) on the pathological complete response (pCR) rate in patients with resectable NSCLC

Secondary objectives 9

1. to assess the effect of neoadjuvant SG plus ZIM on the rate of major pathological response in the resected primary tumor and all resected lymph nodes,
2. to assess the objective response rate following completion of neoadjuvant therapy assessed by imaging using RECIST 1.1,
3. to assess the rate of nodal downstaging, defined as the reduction from clinical nodal positive (cN+) to pathologic nodal negative (ypN0) according to histopathological analysis,
4. to assess the time to surgery from the last dose of neoadjuvant treatment, i.e. from C4D8,
5. to assess the surgical resection rate,
6. evaluate the effect of neoadjuvant SG plus ZIM followed by adjuvant ZIM with or without SG on disease-free survival (inclusion to any recurrence of disease or death from any cause in the intent-to-treat population),
7. evaluate overall survival
8. evaluate safety
9. evaluate quality of life

Conditions and MedDRA coding

non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patients ≥ 18 years of age at the time of informed consent signature.
2. 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.
3. 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).
4. Adequate liver function (bilirubin ≤ 1.5 ULN, AST and ALT ≤ 2.5 x ULN)
5. Creatinine clearance ≥ 30 mL/min as assessed by the CKD-EPI method.
6. Patients are amenable to neoadjuvant treatment followed by surgery and adjuvant treatment.
7. ECOG 0-1
8. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
9. 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 20

1. 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.
2. Has previously received topoisomerase 1 inhibitors.
3. 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.
4. 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.
5. 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.
6. 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).
7. Medication that is known to interfere with any of the agents applied in the trial.
8. 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.
9. Has received prior radiotherapy of the primary tumor and/or mediastinum.
10. 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
11. Has previously received topoisomerase 1 inhibitors
12. 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.
13. 13. 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.
14. 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.
15. 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).
16. Medication that is known to interfere with any of the agents applied in the trial.
17. 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.
18. Any condition or disease, which might interfere with the subject's ability to comply with the study procedures (e.g. dementia).
19. Has been incarcerated or involuntarily institutionalized by court order or by the authorities.
20. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pathological complete response (pCR) rate in the resected primary tumor and all resected lymph nodes, defined as the proportion of patients whose resected samples are negative for residual viable tumor cells

Secondary endpoints 5

1. Major pathological response (MPR) rate in the resected primary tumor and all resected lymph nodes (defined as the proportion of patients whose resected samples show 10% or less residual viable tumor cells)
2. Objective response rate (ORR) following completion of neoadjuvant therapy assessed by imaging using RECIST 1.1. Surgical resection rate. Time to surgery following C4D1
3. Disease-free survival, DFS (inclusion to any recurrence of disease or death from any cause in the intent-to-treat population)
4. Overall survival, OS (inclusion to death from any cause in the intent-to-treat population). Adverse events, AE (CTCAE 5)
5. Quality of life, QoL (EORTC-QLQ-C30 and EQ-5D-5L)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AIO-Studien gGmbH

Sponsor organisation

AIO-Studien gGmbH

Address

Kuno-Fischer-Strasse 8, Charlottenburg Charlottenburg

City

Berlin

Postcode

14057

Country

Germany

Scientific contact point

Organisation

AIO-Studien gGmbH

Contact name

Katrin Krause

Public contact point

Organisation

AIO-Studien gGmbH

Contact name

Katrin Krause

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications