Toripalimab Plus Sacituzumab Tirumotecan as Neoadjuvant Therapy for Resectable NSCLC

A Phase II Study of Toripalimab Combined With Sacituzumab Tirumotecan as Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer

This is a prospective, multicenter, single-arm Phase II investigator-initiated trial evaluating neoadjuvant toripalimab plus sacituzumab tirumotecan (SKB264) in treatment-naive adults with resectable or potentially resectable, driver-negative non-small cell lung cancer (NSCLC). Eligible participants have stage II-IIIA or selected IIIB disease (T3N2 or T4N2) and will receive sacituzumab tirumotecan 5 mg/kg plus toripalimab 3 mg/kg intravenously on Day 1 every 2 weeks for up to 6 cycles. Participants deemed operable after multidisciplinary assessment will undergo definitive surgery. The primary endpoint is pathologic complete response. A Simon two-stage minimax design plans to enroll 30 participants.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Toripalimab; Drug: Sacituzumab Tirumotecan (SKB264)

Detailed Description

This prospective, multicenter, single-arm Phase II investigator-initiated trial evaluates neoadjuvant sacituzumab tirumotecan (SKB264), a TROP2-directed antibody-drug conjugate, plus the PD-1 antibody toripalimab in treatment-naive adults with resectable or potentially resectable, driver-negative NSCLC. Participants have stage II-IIIA or selected IIIB disease (T3N2 or T4N2). Sacituzumab tirumotecan 5 mg/kg and toripalimab 3 mg/kg are administered intravenously on Day 1 every 2 weeks for up to 6 cycles. Surgery is planned 4-6 weeks after the final neoadjuvant dose when the participant remains operable following multidisciplinary assessment. Tumor response is assessed using RECIST 1.1. Safety is assessed using NCI CTCAE version 5.0, including adverse events, serious adverse events, perioperative complications, and surgery delays or cancellations. The primary endpoint is pathologic complete response, defined as no residual viable tumor cells in the resected primary tumor and all resected lymph nodes. Major pathologic response is defined as residual viable tumor of 10% or less.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shaodong Hong Hong, M.D., Ph.D.; Phone Number: +8615920527656; Email: hongshd@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent obtained before any study procedure.
• Age 18 to 75 years, male or female.
• Histologically/cytologically confirmed, treatment-naive, resectable or potentially resectable NSCLC: stage II-IIIA and selected IIIB (T3N2, T4N2) per IASLC/UICC TNM 9th edition.
• Disease staged as cTNM by PET-CT or by neck/chest/abdominal/pelvic CT plus whole-body bone scan and brain MRI.
• Multidisciplinary team including thoracic surgeon judges lesion resectable or potentially resectable.
• At least one measurable target lesion per RECIST 1.1.
• ECOG performance status 0-1.
• Adequate organ function (baseline, no transfusion, rh-EPO, or G-CSF within 2 weeks before first dose): neutrophils ≥1.5 ×10^9/L; platelets ≥100 ×10^9/L; hemoglobin ≥9 g/dL.
• AST, ALT, ALP ≤2.5 × ULN; TBil ≤1.5 × ULN.
• For liver metastases: AST/ALT ≤5 × ULN; TBil ≤2 × ULN.
• For liver or bone metastases: ALP ≤5 × ULN.
• Creatinine clearance (Cockcroft-Gault) ≥60 mL/min.
• INR, APTT, PT ≤1.5 × ULN.
• TSH within normal range; if TSH abnormal but T3 and free T4 normal, eligible.
• Women of childbearing potential must have a negative pregnancy test within 7 days before first dose and use effective contraception during treatment and until 12 months after last dose; men with partners of childbearing potential must use effective contraception during treatment and until 12 months after last dose.

Exclusion Criteria:

• Neuroendocrine histology component in tumor pathology.
• Known EGFR sensitizing mutation or ALK fusion (for non-squamous NSCLC, EGFR/ALK status must be determined).
• Other malignancy within 5 years, except those with clinically negligible metastatic risk and curative treatment intent (e.g., adequately treated carcinoma in situ as per protocol examples).
• Severe or uncontrolled comorbidities, including symptomatic cerebrovascular events or liver disease at Child-Pugh grade ≥A.
• History of allogeneic stem cell transplantation or solid organ transplantation.
• Severe dry eye syndrome, severe meibomian gland dysfunction, severe blepharitis, or corneal disorders that may delay corneal healing.
• History of interstitial lung disease requiring steroids, or active ILD.
• HIV positive or diagnosed AIDS.
• Active tuberculosis.
• Uncontrolled active HBV infection (HBsAg positive with HBV-DNA above local upper limit of normal). HBV-DNA must be <500 IU/mL within 28 days before randomization/inclusion.
• Active HCV infection (HCV antibody positive and HCV RNA positive).
• Known hypersensitivity to toripalimab or sacituzumab tirumotecan (or excipients).
• Live vaccine within 30 days before first dose (except inactivated vaccines allowed where specified by protocol, including local policy).
• Any systemic or local anticancer treatment before first study treatment.
• Use of traditional Chinese medicines with anticancer indication within 7 days before first dose, or need to continue such drugs during study.
• Other investigational drug not discontinued for at least 5 half-lives or 2 months (whichever is longer) before first dose.
• Any known or suspected autoimmune disease or immunodeficiency, except primary hypothyroidism (stable, not requiring hormones, or stable on physiologic hormone replacement) and stable type 1 diabetes mellitus with controlled blood glucose.
• Medical or psychiatric conditions likely to cause premature discontinuation or compromise safety, sampling, or follow-up, including severe social or compliance risks.
• Pregnancy or breastfeeding; unwillingness to use effective contraception as specified.
• Any other condition considered unsuitable by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Toripalimab plus sacituzumab tirumotecan; Participants will receive sacituzumab tirumotecan 5 mg/kg intravenously on Day 1 every 2 weeks combined with toripalimab 3 mg/kg intravenously on Day 1 every 2 weeks for up to 6 cycles as neoadjuvant therapy. Surgery will be performed after multidisciplinary assessment when appropriate. Postoperative or adjuvant treatment will be determined according to guidelines and investigator assessment.

Drug: Toripalimab; Toripalimab 3 mg/kg intravenously on Day 1 every 2 weeks for up to 6 cycles as neoadjuvant therapy, administered in combination with sacituzumab tirumotecan.; Drug: Sacituzumab Tirumotecan (SKB264); Sacituzumab tirumotecan (SKB264) 5 mg/kg intravenously on Day 1 every 2 weeks for up to 6 cycles as neoadjuvant therapy, administered in combination with toripalimab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate	Proportion of participants with no residual viable tumor cells in the resected primary tumor and all resected lymph nodes. Participants without surgery or evaluable surgical pathology will be counted as non-pCR.	At definitive surgery, up to 18 weeks after first study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR) Rate	Proportion of participants with residual viable tumor of 10% or less in the resected primary tumor and all resected lymph nodes.	At definitive surgery, up to 18 weeks after first study treatment
R0 Resection Rate	Proportion of participants who undergo R0 resection, defined as microscopically margin-negative resection, after neoadjuvant therapy.	At definitive surgery, up to 18 weeks after first study treatment
Pathological Downstaging Rate	Proportion of participants with pathological stage lower than baseline clinical stage at definitive surgery.	At definitive surgery, up to 18 weeks after first study treatment
Objective Response Rate (ORR)	Proportion of participants with complete response or partial response according to investigator-assessed RECIST 1.1 after neoadjuvant therapy.	Up to 18 weeks after first study treatment
Event-Free Survival (EFS)	Time from enrollment to disease progression precluding surgery, disease progression or recurrence after surgery, disease progression in participants who do not undergo surgery, or death from any cause, whichever occurs first.	Up to 60 months from enrollment
Overall Survival (OS)	Time from enrollment to death from any cause.	Up to 60 months from enrollment
Incidence of Adverse Events	Incidence of adverse events graded according to NCI CTCAE version 5.0.	From first study treatment through 90 days after the last study treatment or surgery, whichever occurs later

Collaborators and Investigators

• Sponsor: Shaodong Hong
• Collaborators: Shanghai Junshi Bioscience Co., Ltd.; Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 24, 2026
• First Submitted That Met QC Criteria: September 13, 2026
• First Posted (Actual): September 15, 2026

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 13, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Neoadjuvant Therapy; Toripalimab; Resectable NSCLC; Sacituzumab Tirumotecan
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; toripalimab
• Other Study ID Numbers: 2026-FXY-019-NEIKE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data and data dictionaries from this investigator-initiated Phase II oncology study will not be shared at this time due to current sponsor/institutional policy, data governance requirements, and pending legal/ethics arrangements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No