The goal of this Phase II clinical trial (The PHOENIX Study) is to evaluate if the combination of QL1706 (Iparomlimab and Tuvonralimab), bevacizumab, and chemotherapy can treat patients with TKI-refractory, driver-gene positive (e.g., EGFR, ALK, ROS1, RET, KRAS, BRAF, HER2), non-squamous non-small cell lung cancer (NSCLC) who have high PD-L1 expression (TPS ≥50%).
The main question\[s\] it aims to answer \[is/are\]:
Does the quadruple combination therapy improve the Objective Response Rate (ORR) compared to historical chemotherapy data? What are the secondary efficacy outcomes, including Progression-Free Survival (PFS) and Overall Survival (OS)?
If there is a comparison group: There is no concurrent control group (this is an open-label, multi-cohort study). Researchers will compare the treatment outcomes of the participants to historical control data (standard platinum-based chemotherapy) to see if the objective response rate (ORR) improves from a historical baseline of 29% to a target of 55%.
Participants will:
Receive induction therapy every 3 weeks for 4 cycles, consisting of intravenous infusions of QL1706, bevacizumab, pemetrexed, and platinum chemotherapy (cisplatin or carboplatin).
Receive maintenance therapy every 3 weeks with QL1706 and bevacizumab for up to 2 years or until disease progression.
Undergo regular tumor assessments (CT or MRI scans) to monitor disease status according to RECIST v1.1 criteria.
Provide blood samples for safety monitoring and potential biomarker analysis.
None
Prior treatment with QL1706 or other investigational PD-1/PD-L1/CTLA-4 antibodies, unless allowed by the protocol.
Untreated or symptomatic central nervous system (CNS) metastases. Participants with previously treated, stable, and asymptomatic CNS metastases off steroids for at least 2 weeks before first dose may be eligible.
History of severe allergic reactions or hypersensitivity to monoclonal antibodies, platinum agents, pemetrexed, bevacizumab, or any excipients of the study drugs.
Uncontrolled hypertension despite optimal medical management
Parallel
QL1706 (bispecific antibody targeting PD-1 and CLTA-4)
DrugAll cohorts will receive the same treatment regimen in 3-week cycles.Participants will receive combination therapy, consisting of QL1706 (5.0 mg/kg, day 1), bevacizumab (7.5 mg/kg, days1), pemetrexed(500 mg/m², days1) and Platinum \[Cisplatin (75 mg/m²) or Carboplatin (AUC 5/mg/ml, up to 750 mg), Day 1\],intravenously every 3 weeks for four cycles in induction phase, followed by QL1706 (5.0 mg/kg, day 1) and bevacizumab (7.5 mg/kg, days1) every 3 weeks for up to 2 years or until disease progression
Objective Response Rate (ORR) per RECIST 1.1
Objective Response Rate (ORR) is defined as the proportion of participants who achieve a best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1, as assessed by the investigator.
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from randomization to the first documented disease progression per RECIST 1.1 or death from any cause, whichever occurs first, as assessed by the investigator.
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Guangdong Association of Clinical Trials
Lead sponsor
Guangdong Provincial People's Hospital
Sponsor institution
Qilu Pharmaceutical Co., Ltd.
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
