A Trial of GFH018 and Toripalimab in Combination With Concurrent Chemoradiotherapy in Stage III NSCLC Chemoradiotherapy in Stage III NSCLC

Study Overview
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Brief Summary
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This is a phase II trial assessing the efficacy and safety of GFH018 and Toripalimab in combination with concurrent chemoradiotherapy (cCRT) in patients with unresectable, locally advanced, Stage III non-small cell lung cancer (NSCLC).

Official Title
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A Phase 2 Trial of GFH018 and Toripalimab in Combination With Concurrent Chemoradiotherapy for Patients With Unresectable, Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC)

Conditions
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NSCLC, Stage III

Intervention / Treatment
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* Drug: GFH018
* Drug: Toripalimab
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Pemetrexed
* Radiation: Thoracic Radiation Therapy (TRT)
* Drug: GFH018


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Newly diagnosed, pathologically (histologically or cytologically) confirmed, locally advanced, unresectable stage III NSCLC Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Measurable disease (according to RECIST v1.1 criteria) Life expectancy > 6 months Exclusion Criteria: Has small cell lung cancer (SCLC) or tumors with the presence of small cell elements. Has received prior treatment (chemotherapy, targeted therapy, or radiotherapy) for Stage III NSCLC Prior exposure to immune-mediated therapy, including but not limited to, TGFβ inhibitors, anti CTLA-4, anti-PD-1, anti-PD-L1, and anti PD L2 antibodies. Known allergy or hypersensitivity to any of the IPs or any of the IP excipients. Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving ≥20 Gy in total (V20) of more than 35% of lung volume.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Primary Purpose: ORR
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br>GFH018 80mg 7-Day on/ 7-Day off and 4 doses of Toripalimab 240mg Q3W concurrently with standard chemo-radiotherapy, followed by GFH018 80mg 14-Day on/ 14-Day off and Toripalimab 3mg/kg Q2W for up to 48 weeks | Drug: GFH018<br>* Administered as oral<br>Drug: Toripalimab<br>* Administered as an IV infusion<br>Drug: Paclitaxel<br>* Administered as an IV infusion<br>Drug: Carboplatin<br>* Administered as an IV infusion<br>Drug: Cisplatin<br>* Administered as an IV infusion<br>Drug: Pemetrexed<br>* Administered as an IV infusion<br>Radiation: Thoracic Radiation Therapy (TRT)<br>* Thoracic Radiation Therapy (TRT)<br>Drug: GFH018<br>* Administered as an IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate (ORR) is defined as the percentage of patients with objective response (OR). OR was determined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). OR is defined as the best overall response (Complete Response (disappearance of all target and non-target lesions; no new lesions) or Partial Response (≥decrease in the sum of the largest diameters of target lesions; no new lesions)) across all assessment points from enrollment to termination of trial treatment. Radiological tumour assessment was performed using CT scans. | From the date of enrolment of the first patient up to 28 months , which is also16 months after the enrolment of the last patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally Advanced, Unresectable NSCLC, TGF-βRI, PD-1