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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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.
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.
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.
Time frame: At definitive surgery, up to 18 weeks after first study treatment
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 60 months from enrollment
Overall Survival (OS)
Time from enrollment to death from any cause.
Time frame: Up to 60 months from enrollment
Incidence of Adverse Events
Incidence of adverse events graded according to NCI CTCAE version 5.0.
Time frame: From first study treatment through 90 days after the last study treatment or surgery, whichever occurs later
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