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Extrapulmonary Neuroendocrine Carcinoma (EP-NEC)Phase 2NCT07738159

Iparomlimab and Tuvonralimab (QL1706) Plus Lenvatinib and Chemotherapy for Extrapulmonary Neuroendocrine Carcinoma

A Phase 2 study testing Iparomlimab and tuvonralimab injection (QL1706) + Lenvatinib + EP/EC and EP/EC in people with Extrapulmonary Neuroendocrine Carcinoma (EP-NEC) and QL1706, run by West China Hospital.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
Search all trials

Trial summary

The aim of this prospective, randomized, controlled clinical trial is to evaluate the efficacy and safety of iparomlimab and tuvonralimab injection (QL1706) plus lenvatinib and etoposide-based platinum chemotherapy, consisting of etoposide plus cisplatin or carboplatin, compared with etoposide-based platinum… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Iparomlimab and tuvonralimab injection (QL1706) + Lenvatinib + EP/EC and EP/EC
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
No sites listed yet
Study dates
1 Aug 2026to 1 Sep 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically and/or cytologically confirmed locally advanced unresectable or metastatic extrapulmonary neuroendocrine carcinoma. Eligible primary sites include the gastrointestinal tract, pancreas, biliary tract, and other extrapulmonary organs. Neuroendocrine carcinoma of the digestive system must be diagnosed according to the 2019 World Health Organization Classification of Tumours of the Digestive System.
  • Age ≥18 years, with no restriction on sex.
  • Life expectancy of at least 12 weeks.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
  • Patients must not have received prior first-line systemic anticancer therapy for advanced or metastatic disease. Patients who previously received adjuvant therapy following curative surgery are eligible, provided that disease recurrence occurred more than 6 months after completion of adjuvant therapy.
  • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
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  • No severe complications related to the primary tumor, including perforation, obstruction, or major bleeding that cannot be adequately controlled with medical treatment.
  • Adequate organ function, as demonstrated by the following laboratory results obtained within 7 days before enrollment. Patients must not have received blood transfusion, granulocyte colony-stimulating factor (G-CSF), or other supportive treatment affecting the relevant laboratory parameters within 14 days before the first dose of study treatment: Hemoglobin ≥90 g/L; Platelet count ≥75 × 10⁹/L; White blood cell count ≥3.0 × 10⁹/L; Absolute neutrophil count ≥1.5 × 10⁹/L; Total bilirubin ≤1.5 × the upper limit of normal (ULN); Serum creatinine ≤1.5 × ULN; Alanine aminotransferase and aspartate aminotransferase ≤2.5 × ULN, or ≤5 × ULN in participants with liver metastases.
  • Participants with active hepatitis B virus or hepatitis C virus infection must have received antiviral therapy for at least 14 days before the first dose of study treatment. Hepatitis B virus DNA must be ≤500 IU/mL or ≤2,500 copies/mL, and hepatitis C virus RNA must be below the lower limit of detection of the applicable assay. Such participants must be willing to continue effective antiviral treatment throughout the study.
  • Voluntary participation in the study and provision of written informed consent.

Who cannot join

  • Histologically confirmed neuroendocrine tumor, mixed adenoneuroendocrine carcinoma, or other non-neuroendocrine carcinoma pathological types.
  • History of another malignancy with a disease-free interval of less than 5 years, except for adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, or a gastrointestinal tumor confirmed to have been cured by endoscopic mucosal resection.
  • Uncontrolled hypertension despite medical treatment, defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg.
  • Urine protein ≥2+ on routine urinalysis or 24-hour urinary protein ≥1 g.
  • Major surgery within 4 weeks before enrollment, excluding diagnostic biopsy, or an incompletely healed surgical wound.
  • Severe gastrointestinal disorders that may affect drug absorption, including but not limited to peptic ulcer, ulcerative colitis, active gastrointestinal bleeding, gastrointestinal obstruction, or severe diarrhea.
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  • A history of severe bleeding within the previous 3 months, defined as a single bleeding episode of >30 mL; hemoptysis within the previous 1 month, defined as a single episode of >5 mL; or a thromboembolic event within the previous 12 months, including pulmonary embolism or cerebral infarction.
  • Severe cardiovascular disease, including but not limited to acute myocardial infarction, unstable angina, heart failure, ventricular arrhythmia requiring medical treatment, left ventricular ejection fraction <50%, or New York Heart Association cardiac functional class II or higher.
  • Corrected QT interval (QTc) >480 ms on electrocardiography.
  • Active autoimmune disease, a history of autoimmune disease with a risk of recurrence, or another condition requiring immunosuppressive treatment, such as prior organ transplantation. Participants with type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, or skin disorders not requiring systemic treatment, such as vitiligo, psoriasis, or alopecia, may be enrolled.
  • A history of interstitial lung disease or noninfectious pneumonitis that is symptomatic, or a previous pulmonary condition that may interfere with the evaluation or management of study treatment-related pulmonary toxicity.
  • Active pulmonary tuberculosis within 1 year before the first dose of study treatment. Patients with a history of active pulmonary tuberculosis more than 1 year before the first dose must undergo careful evaluation, including sputum smear examination, T-SPOT.TB testing, erythrocyte sedimentation rate testing, and chest computed tomography. Such participants may be enrolled only if there is no evidence of active pulmonary tuberculosis.
  • A history of chronic persistent diarrhea or the presence of complete intestinal obstruction.
  • Requirement for systemic treatment with corticosteroids at a prednisone-equivalent dose of >10 mg/day or other immunosuppressive agents within 14 days before the first dose of study treatment. Inhaled or topical corticosteroids and adrenal replacement therapy at a prednisone-equivalent dose of ≤10 mg/day are permitted in the absence of active autoimmune disease. Short-term corticosteroid use for ≤7 days is permitted for prophylaxis, such as prevention of contrast-media allergy, or for the treatment of non-autoimmune conditions, such as delayed hypersensitivity caused by contact allergens.
  • Prior treatment with any antibody or drug targeting a T-cell co-regulatory protein or immune checkpoint, including but not limited to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-OX-40, anti-CD137, anti-TIM-3, or anti-LAG-3 therapies.
  • Immunodeficiency disorder or human immunodeficiency virus infection.
  • Severe medical or surgical comorbidities that impair organ function, or an acute infection associated with a body temperature >38°C, which, in the investigator's judgment, would make the patient unsuitable for the study.
  • Leptomeningeal metastases or symptomatic brain metastases.
  • Pregnant or breastfeeding women, or patients of reproductive potential, including male patients and women who have been postmenopausal for less than 1 year, who are unwilling to use effective contraception.
  • A history of allergy or hypersensitivity to any component of the study treatments.
  • Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study.

About this study

Official title: A Prospective, Randomized, Controlled Clinical Trial of Iparomlimab and Tuvonralimab Injection (QL1706) Plus Lenvatinib and Chemotherapy as First-Line Treatment for Extrapulmonary Neuroendocrine Carcinoma

The aim of this prospective, randomized, controlled clinical trial is to evaluate the efficacy and safety of iparomlimab and tuvonralimab injection (QL1706) plus lenvatinib and etoposide-based platinum chemotherapy, consisting of etoposide plus cisplatin or carboplatin, compared with etoposide-based platinum chemotherapy alone as first-line treatment for patients with extrapulmonary neuroendocrine carcinoma. Potential predictive biomarkers will also be explored through analyses of tumor tissue, peripheral blood, and relevant clinical and pathological data.

Read the detailed description

This is a prospective, randomized, controlled clinical trial evaluating iparomlimab and tuvonralimab (QL1706) plus lenvatinib and platinum-etoposide chemotherapy as first-line treatment for patients with unresectable or metastatic extrapulmonary neuroendocrine carcinoma.

The study includes a safety lead-in phase and a randomized phase. During the safety lead-in phase, six participants will receive QL1706 plus lenvatinib and platinum-etoposide chemotherapy. Dose-limiting toxicities will be evaluated. If two or more participants experience a dose-limiting toxicity, the starting dose of lenvatinib in the randomized phase will be reduced from 8 mg to 4 mg once daily.

In the randomized phase, eligible participants will be assigned to receive either QL1706 plus lenvatinib and platinum-etoposide chemotherapy or platinum-etoposide chemotherapy alone. After six cycles of combination treatment, participants in the experimental group will receive maintenance treatment with QL1706 plus lenvatinib until disease progression, unacceptable toxicity, or another protocol-defined reason for discontinuation. Participants in the control group will enter follow-up observation after completing six cycles of chemotherapy.

The study will evaluate treatment efficacy and safety, including the 6-month PFS rate, PFS, OS, tumor response, duration of response, and treatment-related adverse events. Potential predictive biomarkers will also be explored using tumor tissue, peripheral blood, and relevant clinical and pathological data.

Being tested
Iparomlimab and tuvonralimab injection (QL1706) + Lenvatinib + EP/EC, EP/EC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iparomlimab and tuvonralimab injection (QL1706) + Lenvatinib + EP/ECDrug

    Participants will receive iparomlimab and tuvonralimab injection (QL1706) at 5 mg/kg intravenously on Day 1, etoposide at 100 mg/m² intravenously on Days 1-3, and either cisplatin at 75 mg/m² intravenously per cycle or carboplatin at AUC 5 intravenously on Day 1 of each 21-day cycle. Lenvatinib will be administered orally once daily at 8 mg or 4 mg, as determined by the safety findings from the safety run-in phase. After six cycles of combination treatment, participants without disease progression or unacceptable toxicity will continue maintenance treatment with QL1706 plus lenvatinib until disease progression, unacceptable toxicity, or another protocol-defined reason for discontinuation.

  • EP/ECDrug

    Patients will receive etoposide 100 mg/m² intravenously on Days 1-3, together with either cisplatin 75 mg/m² intravenously per cycle or carboplatin AUC 5 intravenously on Day 1 of each 21-day cycle.

Study groups in NCT07738159
Study groupRoleWhat they receive
Iparomlimab and tuvonralimab injection (QL1706) + Lenvatinib + EP/ECExperimentalThis arm includes a safety run-in cohort followed by a randomized experimental cohort. In the safety run-in, six participants will receive iparomlimab and tuvonralimab (QL1706), lenvatinib 8 mg once daily, and etoposide plus cisplatin or carboplatin. If DLTs occur in at least 2 of the 6 participants, the starting lenvatinib dose in the randomized experimental cohort will be reduced to 4 mg once daily; otherwise, 8 mg once daily will be used. Participants in the randomized experimental cohort will receive six cycles of combination treatment, followed by maintenance QL1706 plus lenvatinib until disease progression, unacceptable toxicity, or treatment discontinuation.
Receives: Drug: Iparomlimab and tuvonralimab injection (QL1706) + Lenvatinib + EP/EC
EP/ECActive comparatorParticipants in the randomized control arm will receive etoposide plus cisplatin or carboplatin as first-line treatment for six cycles, followed by observation and follow-up.
Receives: Drug: EP/EC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 6-month PFS rate

    The 6-month PFS rate is defined as the proportion of patients who are alive and free from radiographic disease progression at 6 months after enrollment, as assessed by blinded independent radiologic review. Disease progression or death from any cause, whichever occurs first, will be considered a progression-free survival event.

    Measured: Up to 24 months

Secondary outcomes (5)
  1. PFS

    PFS is defined as the time from enrollment to the first documented radiographic disease progression, as assessed by blinded independent radiologic review, or death from any cause, whichever occurs first.

    Measured: 2 years

  2. OS

    OS is defined as the time from enrollment to death from any cause.

    Measured: 2 years

  3. ORR

    ORR is defined as the proportion of patients whose best overall response is complete response or partial response, as assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent radiologic review.

    Measured: 2 years

  4. DCR

    DCR is defined as the proportion of participants whose best overall response is complete response, partial response, or stable disease, as assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent radiologic review.

    Measured: 2 years

  5. DoR

    DoR is defined as the time from the first documented complete response or partial response to the first documented radiographic disease progression, as assessed by blinded independent radiologic review according to Response Evaluation Criteria in Solid Tumors version 1.1 or death from any cause, whichever occurs first.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2026
  2. Study start1 Aug 2026 (estimated)
  3. Primary completion1 Aug 2030 (estimated)
  4. Study completion1 Sep 2030 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Model description
This study consists of a non-randomized safety run-in phase followed by a randomized, controlled, parallel-group phase. In the safety run-in phase, six participants will receive iparomlimab and tuvonralimab injection (QL1706) plus lenvatinib 8 mg orally once daily and etoposide with cisplatin or carboplatin. If dose-limiting toxicities (DLTs) are observed in at least 2 of the 6 participants during the prespecified DLT assessment period, the lenvatinib dose in the experimental arm of the subsequent randomized phase will be reduced to 4 mg once daily; otherwise, the 8 mg once-daily dose will be retained. After completion of the safety run-in phase, eligible participants will be randomized to receive either QL1706 plus lenvatinib and etoposide with cisplatin or carboplatin, or etoposide with cisplatin or carboplatin alone.
Masking
None (open label)
Enrolment
92 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07738159
Sponsor's protocol ID
2026(1754)
Status last verified
Jul 2026
First submitted
25 Jul 2026
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Iparomlimab and tuvonralimab injection (QL1706) + Lenvatinib + EP/EC and EP/EC in people with Extrapulmonary Neuroendocrine Carcinoma (EP-NEC) and QL1706, run by West China Hospital.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6-month PFS rate (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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