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

NCT06028633 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: MISP61001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Non-squamous Non-small-cell Lung Cancer; Recurrent Non-Squamous Non-Small Cell Lung Cancer; Metastatic Non-squamous Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Objective response rate (ORR) assessed per the Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)

  About 18 months

Secondary Outcomes (4)

• Overall survival

  About 36 months

• Progression-free survival

  About 24 months

• Duration of response

  About 24 months

• Treatment-related adverse events

  About 24 months

Other Outcomes (1)

• Single cell sequencing of tumor specimens

  About 36 months

Study Arms (1)

Arm I

EXPERIMENTAL

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).

Drug: pembrolizumab; Drug: lenvatinib; Drug: albumin-bound paclitaxel

Interventions

pembrolizumab DRUG

pembrolizumab 200mg IV on day 1 for every 3 weeks

Also known as: Keytruda

Arm I

lenvatinib DRUG

lenvatinib 8mg taken orally every day

Also known as: Lenvima

Arm I

albumin-bound paclitaxel DRUG

albumin-bound paclitaxel IV 100mg/m2 D1, 8 every 3 weeks

Also known as: nab-paclitaxel, paclitaxel for injection(albumin bound)

Arm I

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent (ICF) with histologically confirmed diagnosis of metastatic nonsquamous NSCLC (AJCC Staging Manual, Version 8) will be enrolled in this study.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male participants are eligible to participate the study if they agree to the following during the intervention period and for at least 180 days after the last dose of study intervention:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR must agree to use contraception unless confirmed to be azoospermia (vasectomized or secondary to medical cause) as:
• A. Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
• B. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
• C. Please note that 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed D. Refrain from donating sperm for at least 120 days after the last dose of Lenvatinib.
• Female participant is eligible to participate if she is not pregnant or not breastfeeding, and at least one of the following conditions applies:
• A. Not a woman of childbearing potential (WOCBP).
• B. A WOCBP who agrees to follow the contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the treatment period and for at least 120 days after the last dose of pembrolizumab or 30 days after the last dose of lenvatinib, study treatment, and agrees not to donate eggs (ova, oocytes) to others or freeze/store these for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention.
• C. A WOCBP must have negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
• D. If a urine test cannot be confirmed as negative (i.e., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered in combination with platinum doublet chemotherapy concomitantly as first line treatment. Participants who have received Anti-PD-1/PD-L1(either as monotherapy or in combination with chemotherapy) as initial treatment at early-stage or locally advanced NSCLC should NOT be enrolled in this study. Anti-PD-1/PD-L1 treatment progression is defined by meeting all of the following criteria:
• A. Has received at least 2 doses of an approved anti-PD-1/L1 mAb
• B. Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression. Eligible participants should have at least 2 pre-study images as confirmed evidence of PD (assessed by investigator) on treatment of anti-PD-1/L1 mAb before the study intervention.

You may not qualify if:

• 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.
• 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.
• Has received prior Paclitaxel, Docetaxel or Albumin-paclitaxel as monotherapy or in combination with other therapies at any stage of disease.
• 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.
• 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.
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• 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.
• Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
• 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.
• 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.
• Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
• 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.
• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Peking University First Hospital Ethics Committee

Beijing, Beijing Municipality, 100034, China

Location

MeSH Terms

Interventions

pembrolizumab; lenvatinib; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Shikai Wu

  Peking Univerisity First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shikai Wu

CONTACT

(86)18910715326; skywu4329@sina.com

Yan Zhu

CONTACT

(86)13901083721; zhuyan0302@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: September 8, 2023
• Study Start: October 1, 2023
• Primary Completion: October 1, 2024
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)