Efficacy and Safety of Nab-paclitaxel-Lenvatinib-Pembrolizumab as Second-line Treatment in Advanced NSCLC Patients

Phase 2

Not yet recruiting

• Conditions: Recurrent Non-Squamous Non-Small Cell Lung Cancer; Advanced Non-squamous Non-small-cell Lung Cancer; Metastatic Non-squamous Non Small Cell Lung Cancer
• Interventions: Drug: pembrolizumab; Drug: lenvatinib; Drug: albumin-bound paclitaxel

• Registration Number: NCT06028633
• Lead Sponsor: Peking University First Hospital

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of albumin-bound paclitaxel-lenvatinib-pembrolizumab in advanced nonsquamous NSCLC patients after progression to first-line anti-PD-1/L1 inhibitor with platinum-doublet chemotherapy. All participants will be given with albumin-bound paclitaxel, lenvatinib and pembrolizumab.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-22
• Status Verified: 2023-09
• Study First Submitted QC: 2023-09-07
• Study First Posted: 2023-09-08
• Last Update Submitted: 2023-09-10
• Last Update Posted: 2023-09-13
• Study Start: 2023-10
• Primary Completion: 2024-10
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

Not provided

Exclusion Criteria

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment initiation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

2. Has received prior therapy at any stage of disease with any anti-VEGF-TKIs (i.e. Bevacizumab, Lenvatinib, Anlotinib, Apatinib, etc.) as monotherapy or in combination with an anti-PD-1/L1 inhibitor.

3. Has received prior Paclitaxel, Docetaxel or Albumin-paclitaxel as monotherapy or in combination with other therapies at any stage of disease.

4. Has received prior radiotherapy within 2 weeks of start of study intervention or has received lung radiation therapy >30 Gy within 6 months before the first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

5. Has had major surgery within 3 weeks prior to first dose of study interventions.

   Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.

6. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.

7. Has radiographic evidence of major blood vessel invasion/infiltration. In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta.

   Note: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.

8. Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.

9. Has urine protein ≥1 g/24 hours. Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urine dipstick testing or urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.

10. Has a LVEF below the institutional (or local laboratory) normal range, as determined by echocardiogram (ECHO). OR has Prolongation of QTcF interval to >480 ms according to ECG.

11. Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib

12. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

13. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.

14. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.

    Note: Medically controlled arrhythmia would be permitted.

15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

16. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy. Note: The requirement for no evidence of disease for 3 years does not apply to the NSCLC for which a participant is enrolled in the study. This time requirement also does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.

17. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.

18. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.

19. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

20. Has an active infection requiring systemic therapy.

21. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

22. Has a sensitivity to any of the excipients contained in Albumin-paclitaxel and/or Lenvatinib.

23. Has a known history of Human Immunodeficiency Virus (HIV) infection.

24. Has active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.

    Note: Hepatitis B and C screening tests are not required unless:

    • Known history of HBV and HCV infection
    • As mandated by local health authority

25. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.

26. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

27. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

28. Has had an allogenic tissue/solid organ transplant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	albumin-bound paclitaxel	Participants will receive pembrolizumab IV 200 mg D1 every 3 weeks, lenvatinib 8 mg orally every day, albumin-bound paclitaxel IV 100mg/m2 D1, 8 every 3 weeks,until disease progression, intolerable toxicity, investigator decision, or completion of 35 cycles(for pembrolizumab) and 4-6 cycles(for albumin-bound paclitaxel).
Arm I	pembrolizumab	Participants will receive pembrolizumab IV 200 mg D1 every 3 weeks, lenvatinib 8 mg orally every day, albumin-bound paclitaxel IV 100mg/m2 D1, 8 every 3 weeks,until disease progression, intolerable toxicity, investigator decision, or completion of 35 cycles(for pembrolizumab) and 4-6 cycles(for albumin-bound paclitaxel).
Arm I	lenvatinib	Participants will receive pembrolizumab IV 200 mg D1 every 3 weeks, lenvatinib 8 mg orally every day, albumin-bound paclitaxel IV 100mg/m2 D1, 8 every 3 weeks,until disease progression, intolerable toxicity, investigator decision, or completion of 35 cycles(for pembrolizumab) and 4-6 cycles(for albumin-bound paclitaxel).

Primary Outcome Measures

Name	Time	Method
Objective response rate	About 18 months	Objective response rate (ORR) assessed per the Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)

Secondary Outcome Measures

Name	Time	Method
Overall survival	About 36 months	Overall survival (OS)
Treatment-related adverse events	About 24 months	Treatment-related adverse events (TRAEs) assessed by CTCAE v5.0
Progression-free survival	About 24 months	Progression-free survival (PFS) assessed per RECIST v1.1
Duration of response	About 24 months	Duration of response (DoR) assessed per RECIST v1.1

Trial Locations

Locations (1)

Peking University First Hospital Ethics Committee; 🇨🇳 Beijing, Beijing, China