Oral Paclitaxel Solution With Immunotherapy and Concurrent SBRT as Neoadjuvant Treatment for Older Adults With NSCLC

Condition(s) studied

Investigational drug(s) / intervention(s)

Oral Paclitaxel Solution: Phase I dose levels: 80 mg/m², 120 mg/m², and 160 mg/m², administered orally on Days 1 and 8 of each cycle in divided morning and evening doses. Phase II: oral paclitaxel solution at the RP2D.

PD-1/PD-L1 inhibitor: An PD-1/PD-L1 inhibitor selected by the investigator according to standard of care and administered according to the approved prescribing information

Stereotactic Body Radiotherapy (SBRT): SBRT at 8 Gy per fraction for 3 fractions to the primary lung tumor and selected lymph node regions.

Radical Lung Cancer Surgery: Participants considered operable after neoadjuvant therapy are intended to undergo radical lung cancer surgery.

Stereotactic Body Radiotherapy (SBRT): Participants considered inoperable after neoadjuvant therapy are intended to continue SBRT at radical dose assessed by department of radiotherapy.

Study summary

his multicenter, open-label, single-arm phase I/II trial will evaluate the safety, tolerability, and preliminary efficacy of oral paclitaxel solution combined with an immune checkpoint inhibitor and concurrent stereotactic body radiotherapy (SBRT) as neoadjuvant therapy in patients aged 70 years or older with resectable stage IIA-IIIB non-small cell lung cancer (NSCLC) without sensitizing EGFR, ALK, or ROS1 alterations.

In Phase I, a 3+3 dose-escalation design will evaluate oral paclitaxel at 80, 120, and 160 mg/m² administered orally on Days 1 and 8 of each cycle, divided into morning and evening doses, in combination with an investigator-selected anti-PD-1 or anti-PD-L1 monoclonal antibody and SBRT at 8 Gy in 3 fractions. Phase II will expand enrollment at the recommended Phase II dose (RP2D). The principal efficacy outcome is pathologic complete response after surgery. Other outcomes include major pathologic response, radiographic response, event-free survival, overall survival, surgical resection and R0 resection rates, and exploratory biomarker changes.

Eligibility

Primary outcome measure(s)

• Complete Response (CR) Rate in Phase 2 — 2 weeks (±14 days) after surgery or radical radiotherapy
  The percentage of participants in the Phase 2 operable cohort who achieve a CR according to RECIST v1.1, at the protocol-specified preoperative tumor assessment. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes must have a reduction in the short axis to less than 10 mm. Participants who discontinue treatment, experience disease progression, become unable to undergo the planned response assessment, or have no evaluable post-baseline tumor assessment will be classified as not having achieved a CR.
• Incidence of Grade 3 or Higher Treatment-Related Adverse Events (TRAE) in Phase 1 — First dose up to 1 week (±7 days) after neoadjuvant therapy
  The percentage of participants in the Phase 1 dose-escalation cohort who experience at least one Grade 3 or higher TRAE during the safety assessment period. Adverse events will be graded according to the CTCAE 5.0. The relationship of each adverse event (AE) to oral paclitaxel solution, the anti-PD-1 antibody, radiotherapy, or the combination regimen will be assessed by the investigator.

Trial sites (5)

More Shanghai Pulmonary Hospital, Shanghai, China trials in China

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