PIVOT study is a multicenter, phase I/II clinical study designed to evaluate induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy in patients with unresectable locally advanced non-small cell lung cancer (NSCLC). Phase I consists of a single-arm safety lead-in study evaluating the safety and preliminary efficacy of the investigational regimen. If predefined safety criteria are met, the study proceeds to a phase II randomized controlled trial comparing induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy with the standard PACIFIC regimen. The objective of the phase II study is to determine whether the investigational treatment strategy improves progression-free survival while maintaining an acceptable safety profile compared with the standard PACIFIC regimen.
Age >18 years, male or female, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
Unresectable stage III NSCLC (according to the 8th edition of the AJCC staging system).
No prior exposure to any other anti-tumor therapy.
Presence of small cell carcinoma components in the histological examination results.
Co-occurrence of EGFR mutation, ALK rearrangement, or ROS-1 rearrangement positivity.
History of other primary malignancies, with the following exceptions: Malignancies treated with curative intent with no known active disease and low potential for recurrence for ≥5 years prior to the first dose of investigational product (IP); adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; or adequately treated carcinoma in situ without evidence of disease.
Active or documented history of autoimmune or inflammatory diseases (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [excluding diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, granulomatosis with polyangiitis [Wegener's syndrome], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.).
Parallel
Induction chemoimmunotherapy
DrugPhase I: Patients received platinum-based doublet chemotherapy plus a PD-L1 inhibitor every 3 weeks for 2-4 cycles. Phase II (experimental group): Patients received platinum-based doublet chemotherapy plus a PD-L1 inhibitor every 3 weeks for 2 cycles.
Concurrent chemoradiotherapy (cCRT)
RadiationDefinitive thoracic radiotherapy delivered to the primary tumor and involved lymph nodes with concurrent platinum-based chemotherapy. Radiotherapy is administered at 50-60 Gy in 25-30 fractions using intensity-modulated radiotherapy techniques.
consolidation immunotherapy
DrugPD-L1 inhibitor administered every 3 weeks after completion of radiotherapy for up to 1 year or until disease progression, unacceptable toxicity, or withdrawal of consent.
Incidence of Grade 3 or Higher Treatment-Related Adverse Events
Treatment-related adverse events assessed according to CTCAE version 6.0.
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from treatment initiation to documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Overall Survival (OS)
Overall survival is defined as the time from treatment initiation to death from any cause.
Objective Response Rate (ORR)
Objective response rate is defined as the proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST version 1.1.
Treatment Completion Rate
Proportion of participants who successfully complete the planned induction chemoimmunotherapy, radiotherapy-based treatment (concurrent chemoradiotherapy or carbon-ion radiotherapy), and consolidation immunotherapy according to protocol requirements.
Local Control Rate
Local control rate is defined as the proportion of participants without locoregional disease progression according to RECIST version 1.1 and investigator assessment.
Predictive Value of Minimal Residual Disease (MRD) for Clinical Outcomes
To evaluate whether baseline and dynamic changes in minimal residual disease (MRD) status are associated with treatment response, progression-free survival, and overall survival in participants receiving combined radiotherapy and immunotherapy.
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Shanghai Chest Hospital
Lead sponsor
Sun Yat-Sen University Cancer Center
Collaborator
RenJi Hospital
Collaborator
