NSCLCPhase 2NCT05078931
A Study to Evaluate Pembrolizumab Plus Lenvatinib in PD-L1 Positive TKI Resistant NSCLC Patients
A Phase 2 study testing Pembrolizumab and Lenvatinib in people with NSCLC, run by Shanghai Chest Hospital at 1 site in China.
Trial summary
This study will investigate the efficacy and safety of the combination of pembrolizumab and lenvatinib in PD-L1 positive patients with TKI-resistant EGFR-mutated advanced NSCLC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC
- What is being tested?
- Pembrolizumab and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 27 Oct 2021to 30 Dec 2026
- 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
- Have a histologically or cytologically confirmed stage IV NSCLC by American Joint Committee on Cancer Version 8
- Have confirmation with sensitizing EGFR mutations, either DEL19 or L858R
- Have undergone failure 1-2 prior EGFR-TKI (Osimertinib exposure required for T790M+)
- Have measurable disease based on RECIST 1.1, as determined by the local site.
- Note: Lesions that appear measurable but are situated in a previously irradiated area can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
- Tumor tissue that demonstrates PD-L1 expression in ≥1% of tumor cells (TPS ≥1%) as assessed by IHC 22C3 pharmDx.
- Note: Assessment of PD-L1 expression must be made from provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. (A fine-needle aspirate, frozen sample, plastic embedded sample, cell block, clot, bone, bone marrow, cytologic specimen, or decalcified or formalin-fixed sample that was frozen at any point will not be acceptable for analysis). Formalin-fixed, paraffin-embedded tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
Who cannot join
- Has known untreated central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 4 weeks by repeat imaging (note: repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days before first dose of study intervention.
- Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of study intervention.
- Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy.
- Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
- Note: The time requirement for no evidence of disease for at least 3 years does not apply to the NSCLC for which a participant is enrolled in the study. The 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.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with the 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.
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- Has had an allogeneic tissue/solid organ transplant.
- Has a known history of human immunodeficiency virus (HIV) infection; HIV testing is not required unless mandated by the local health authority.
- Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive or hepatitis B virus [HBV]-DNA detected) or known active hepatitis C virus (HCV, defined as HCV-RNA [qualitative] detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infection.
- Note: No testing for hepatitis B and hepatitis C is required unless mandated by the local health authority.
- Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.
- Has significant cardiovascular impairment within 12 months of the first dose of study intervention, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
- Has not recovered adequately from any toxicity and/or complications from major surgery before starting therapy.
- Has a known history of active tuberculosis (TB).
- Has an active infection requiring systemic therapy.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's cooperation for the requirements of the study.
- Previously had a severe hypersensitivity reaction to treatment with an mAb or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab.
- WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study intervention, another pregnancy test (urine or serum) must be performed and must be negative for the participant to start receiving study intervention.
- 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 study intervention.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University
Shanghai, 200030
About this study
Official title: An Open-label, Single-arm Phase II Study of Pembrolizumab Plus Lenvatinib in PD-L1 Positive Patients With TKI-resistant EGFR-mutated Advanced Non-small Cell Lung Cancer
This study will investigate the efficacy and safety of the combination of pembrolizumab and lenvatinib in PD-L1 positive patients with TKI-resistant EGFR-mutated advanced NSCLC.
Read the detailed description
Tyrosine Kinase Inhibitors (TKIs) are the standard front-line treatment for patients with EGFR sensitive mutations. Even though patients have a better response rate and longer PFS comparing to chemotherapy, drug resistance have been an inevitable issue associated with these drugs. The standard of subsequent treatment for TKI resistance at present is chemotherapy (platinum doublet chemotherapy), which shows limited benefit with ORR 20-30% and PFS nearly 4 months. Therefore, it is essential to develop the novel therapies.
Immune checkpoint therapy, which is based on negative regulatory mechanisms and targeted enhancement of the anti-tumor immune response, is a novel and important therapeutic strategy for lung cancer, especially for those patients with PD-1/PD-L1 positive advanced NSCLC. VEGF signaling regulates immune suppression by promoting the expansion of suppressive immune cell populations. Therefore, modulation of VEGF-mediated immune suppression could potentially augment the immunotherapeutic activity of immune checkpoint inhibitors. Lenvatinib is a multitargeted TKI with anti-tumor activity via inhibiting VEGFR 1-3, FGFR 1-4 and PDGFR. It modulates the cancer immunity associated with a decrease in the population of immunosuppressive tumor-associated macrophages and an increase in interferon-γ-producing CD8+ T cells. The combination of immune check point inhibitors (PD-1/PD-L1 inhibitors) and lenvatinib could be a promising strategy to improve the immunotherapy outcome in lung cancer patients.
- Conditions
- NSCLC
- Being tested
- Pembrolizumab, Lenvatinib
- Keywords
- Pembrolizumab, Lenvatinib, NSCLC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab 200 mg will be administered as a 30-minute IV infusion every 3 weeks for up to 35 cycles
LenvatinibDrug
Also called Lenvima
Lenvatinib 20mg will be administered orally daily.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Lenvatinib in PD-L1 Positive TKI resistant NSCLC patients | Experimental | The PD-L1 positive patients with TKI-resistant EGFR-mutated advanced NSCLC will receive the combination of pembrolizumab and lenvatinib. Receives: Drug: Pembrolizumab; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
the time from the start of intervention to evidence of radiographic progression as defined by RECIST criteria or death from any cause without evidence of disease progression, whichever occurs first. Cases with incomplete follow up or without adequate disease evaluations will be censored at date last documented to be progression free.
Measured: Up to approximately 12 months
Secondary outcomes (3)
Overall survival
the time from the start of treatment until death from any cause.
Measured: Up to approximately 24 months
Objective Response Rate
the proportion of the total number of subjects with a confirmed CR or confirmed PR
Measured: Up to approximately 24 months
Duration of Response
the time from the earliest date of qualifying response until earliest date of PD or death from any cause, whichever comes first.
Measured: 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 posted15 Oct 2021
- Study start27 Oct 2021
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- More trials run by Shanghai Chest HospitalThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open-label, single-arm phase II study of lenvatinib plus pembrolizumab in PD-L1 positive patients with TKI-resistant EGFR-mutated advanced non-small cell lung cancer.
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Chest Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Lu Shun, Shanghai Chest Hospital
- Investigators
- Shun Lu, Principal investigator, Shanghai Chest Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05078931
- Sponsor's protocol ID
- TBA
- Status last verified
- Jul 2025
- First submitted
- 14 Sep 2021
- Last updated
- 30 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-arm Phase II Study of Pembrolizumab Plus Lenvatinib in PD-L1 Positive Patients With TKI-resistant EGFR-mutated Advanced Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05078931
- Acronym / sponsor ID
- TBA
- Conditions
- NSCLC
- Keywords
- Pembrolizumab, Lenvatinib, NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Shanghai Chest HospitalUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 27 Oct 2021 (actual)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 15 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the efficacy and safety of the combination of pembrolizumab and lenvatinib in PD-L1 positive patients with TKI-resistant EGFR-mutated advanced NSCLC.
Detailed description
Tyrosine Kinase Inhibitors (TKIs) are the standard front-line treatment for patients with EGFR sensitive mutations. Even though patients have a better response rate and longer PFS comparing to chemotherapy, drug resistance have been an inevitable issue associated with these drugs. The standard of subsequent treatment for TKI resistance at present is chemotherapy (platinum doublet chemotherapy), which shows limited benefit with ORR 20-30% and PFS nearly 4 months. Therefore, it is essential to develop the novel therapies.
Immune checkpoint therapy, which is based on negative regulatory mechanisms and targeted enhancement of the anti-tumor immune response, is a novel and important therapeutic strategy for lung cancer, especially for those patients with PD-1/PD-L1 positive advanced NSCLC. VEGF signaling regulates immune suppression by promoting the expansion of suppressive immune cell populations. Therefore, modulation of VEGF-mediated immune suppression could potentially augment the immunotherapeutic activity of immune checkpoint inhibitors. Lenvatinib is a multitargeted TKI with anti-tumor activity via inhibiting VEGFR 1-3, FGFR 1-4 and PDGFR. It modulates the cancer immunity associated with a decrease in the population of immunosuppressive tumor-associated macrophages and an increase in interferon-γ-producing CD8+ T cells. The combination of immune check point inhibitors (PD-1/PD-L1 inhibitors) and lenvatinib could be a promising strategy to improve the immunotherapy outcome in lung cancer patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open-label, single-arm phase II study of lenvatinib plus pembrolizumab in PD-L1 positive patients with TKI-resistant EGFR-mutated advanced non-small cell lung cancer.
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Lenvatinib in PD-L1 Positive TKI resistant NSCLC patients | Experimental | Drug: Pembrolizumab, Drug: LenvatinibThe PD-L1 positive patients with TKI-resistant EGFR-mutated advanced NSCLC will receive the combination of pembrolizumab and lenvatinib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Have a histologically or cytologically confirmed stage IV NSCLC by American Joint Committee on Cancer Version 8
- Have confirmation with sensitizing EGFR mutations, either DEL19 or L858R
- Have undergone failure 1-2 prior EGFR-TKI (Osimertinib exposure required for T790M+)
- Have measurable disease based on RECIST 1.1, as determined by the local site.
- Tumor tissue that demonstrates PD-L1 expression in ≥1% of tumor cells (TPS ≥1%) as assessed by IHC 22C3 pharmDx.
Key exclusion criteria (22 listed)
- Has known untreated central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 4 weeks by repeat imaging (note: repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days before first dose of study intervention.
- Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of study intervention.
- Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy.
- Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with the 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaPembrolizumab 200 mg will be administered as a 30-minute IV infusion every 3 weeks for up to 35 cycles | Drug | Pembrolizumab + Lenvatinib in PD-L1 Positive TKI resistant NSCLC patients |
| LenvatinibAlso: LenvimaLenvatinib 20mg will be administered orally daily. | Drug | Pembrolizumab + Lenvatinib in PD-L1 Positive TKI resistant NSCLC patients |
Primary outcome
Progression-free survival
Time frame: Up to approximately 12 months
the time from the start of intervention to evidence of radiographic progression as defined by RECIST criteria or death from any cause without evidence of disease progression, whichever occurs first. Cases with incomplete follow up or without adequate disease evaluations will be censored at date last documented to be progression free.
3 secondary outcomes
Overall survival
Time frame: Up to approximately 24 months
Objective Response Rate
Time frame: Up to approximately 24 months
Duration of Response
Time frame: Up to approximately 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shun Lu principal investigator
Shanghai Chest Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Lenvatinib in people with NSCLC, run by Shanghai Chest Hospital at 1 site in China.
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 7 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Progression-free survival (time frame: Up to approximately 12 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 30 Jul 2025.