Lung AdenocarcinomaPhase 2PHOENIXNCT07416058
PHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC
A Phase 2 study testing QL1706 (bispecific antibody targeting PD-1 and CLTA-4) in people with Lung Adenocarcinoma, run by Guangdong Association of Clinical Trials at 2 sites in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lung Adenocarcinoma
- What is being tested?
- QL1706 (bispecific antibody targeting PD-1 and CLTA-4)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 2 sitesChina
- Study dates
- 30 Apr 2026to 31 Dec 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The study will enroll adult patients (aged 18-75 years) with histologically confirmed locally advanced or metastatic NSCLC (AJCC 9th Edition, Stage IIIB-IVB), and harbor confirmed actionable driver mutations for which targeted therapies are available; these mutations are stratified as follows: EGFR (19del, L858R); ALK, ROS1, RET fusions; KRAS G12C; BRAF V600; and HER2 exon 20 insertions. Patients must have disease progression following at least one line of TKI therapy and a 2-week washout period is required for prior TKI therapy or chemotherapy. Prior immunotherapy is not permitted. PD-L1 tumor proportion score (TPS) ≥ 50%, as confirmed by central laboratory testing using the 22C3 or SP263 clone on fresh or archival tumor tissue (collected within 2 years). Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, and presence of at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Who cannot join
- 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.
- Clinically significant cardiovascular disease, including but not limited to:
- Uncontrolled hypertension despite optimal medical management
- New York Heart Association (NYHA) class III or IV heart failure
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- Unstable angina, myocardial infarction, or stroke within 6 months prior to enrollment
- Significant arrhythmias requiring anti-arrhythmic therapy
- Active or history of autoimmune disease that has required systemic treatment in the past 2 years (e.g., with disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for conditions such as vitiligo, resolved childhood asthma/atopy, or hypothyroidism on stable replacement therapy.
- Active infection requiring systemic therapy, including known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection, unless well controlled according to protocol-defined criteria.
- Significant hemoptysis (e.g., ≥ 2.5 mL of bright red blood) within 3 months prior to enrollment or any evidence of high-risk bleeding or coagulation disorder that would contraindicate bevacizumab.
- Major surgery within 4 weeks before first dose of study treatment or anticipated need for major surgery during the study.
- Pregnant or breastfeeding women.
- Any other serious medical condition, uncontrolled intercurrent illness, psychiatric illness, or social circumstance that, in the opinion of the investigator, would compromise the participant's safety, interfere with study evaluations, or preclude informed consent.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Guangdong Provincial People's Hospital
Guangzhou, Guangdong,China, 510080
- Recruiting
Guangdong Provincial People's Hospital
Guangzhou, Guangdong,China, 510080
Hao Sun Hao Sun, +86 16620178852, sunhao@gdph.org.cn
About this study
Official title: A Multicenter Study of Iparomlimab and Tuvonralimab (QL1706) Plus Platinum-Based Doublet Chemotherapy and Bevacizumab in PD-L1 ≥50% Non-Squamous Non-Small Cell Lung Cancer With Actionable Genomic Alterations (AGA) Resistant to Prior Targeted Therapy
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]:
Read more
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.
- Conditions
- Lung Adenocarcinoma
- Being tested
- QL1706 (bispecific antibody targeting PD-1 and CLTA-4)
- Keywords
- PD-L1, CTLA-4, QL1706
- Medical subject headings
- Adenocarcinoma of Lung, Diabetes Mellitus, Insulin-Dependent, 12
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QL1706 (bispecific antibody targeting PD-1 and CLTA-4)Drug
Also called pemetrexed, Platinum, bevacizumab
All 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
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (EGFR) consists of patients with EGFR-positive | Experimental | Cohort 1 (EGFR) consists of patients with EGFR-positive non-small cell lung cancer (NSCLC) who have failed prior EGFR-tyrosine kinase inhibitor (TKI) therapy Receives: Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4) |
| Cohort 2 (ALK/ROS1/RET) includes patients with sensitive ALK, ROS1, or RET mutations | Experimental | Cohort 2 (ALK/ROS1/RET) includes patients with sensitive ALK, ROS1, or RET mutations who have progressed on prior TKI therapy targeting the respective driver oncogenes, Receives: Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4) |
| Cohort 3 (KRAS/BRAF/HER2) comprises patients with KRAS G12C, BRAF V600, or HER2 exon 20 insertions | Experimental | Cohort 3 (KRAS/BRAF/HER2) comprises patients with KRAS G12C, BRAF V600, or HER2 exon 20 insertions (20ins) (N=15) who have failed prior targeted therapy for these actionable driver mutations. Receives: Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From first dose until disease progression or start of new anti-cancer therapy, up to approximately 24 months.
Secondary outcomes (1)
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.
Measured: From enrollment until disease progression or death, whichever occurs first, up to approximately 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2026
- Study start30 Apr 2026
- Primary completion30 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Association of Clinical Trials
- Sponsor type
- University, hospital or other
- Collaborators
- Qilu Pharmaceutical Co., Ltd.
- Responsible party
- Principal investigator, Jin-Ji Yang, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07416058
- Sponsor's protocol ID
- KY2025-1174-02
- Acronym
- PHOENIX
- Status last verified
- Oct 2026
- First submitted
- 10 Feb 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No