NsclcPhase 2NCT04989322
Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC
A Phase 2 study testing Pembrolizumab, Lenvatinib and Pemetrexed in people with Nsclc and EGFR Activating Mutation, run by Dr Joanne CHIU at 1 site in Hong Kong.
Trial summary
Adding chemotherapy or anti-VEGF to immunotherapy is an emerging strategy to enhance the efficacy of immunotherapy in many cancers. This phase 2 study aims to explore the preliminary efficacy of combination pembrolizumab with lenvatinib and chemotherapy in NSCLC patients with sensitizing EGFR, ALK, or ROS1 genetic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nsclc, EGFR Activating Mutation, EGF-R Positive Non-Small Cell Lung Cancer
- What is being tested?
- Pembrolizumab, Lenvatinib and Pemetrexed
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteHong Kong
- Study dates
- 5 Oct 2021to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
Main Inclusion Criteria:
- Histologically proven NSCLC
- Unresectable or metastatic NSCLC, including squamous cell carcinoma, harboring sensitizing EGFR, ALK, or ROS1 genetic aberrations who have received standard of care targeted therapy and have progressed on treatment. Patients with known T790M mutation should have received osimertinib and failed.
- Measurable disease per RECIST 1.1
- ECOG performance status ≤ 1
- Adequate organ function
- Adequately controlled blood pressure
Main Exclusion Criteria:
- Prior exposure to immunotherapy or chemotherapy
- Active untreated brain metastasis and/or carcinomatous meningitis
- Active, known or suspected autoimmune disease
- History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease
- Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications
- Baseline proteinuria ≥ 1 g/24 hrs
- Electrolyte abnormalities that have not been corrected
- Significant cardiovascular impairment
- Gastrointestinal pathology that might affect the absorption of lenvatinib
- Preexisting grade ≥ 3 gastrointestinal or non gastrointestinal fistula
- Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage
- Radiographic evidence of intratumoral caviations, encasement, or invasion of a major blood vessel
- Known history of tuberculosis
- Active, acute, or chronic clinically significant infections requiring therapy, including hepatitis B, hepatitis C, and HIV
- ECG with long QTc interval ≥ 470 ms
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Open-label Single-arm Study to Evaluate the Combination of Pembrolizumab, Lenvatinib and Chemotherapy in Non-small Cell Lung Cancer (NSCLC) Harbouring Targetable Mutation and Failed Standard Tyrosine Kinase Inhibitors
Adding chemotherapy or anti-VEGF to immunotherapy is an emerging strategy to enhance the efficacy of immunotherapy in many cancers. This phase 2 study aims to explore the preliminary efficacy of combination pembrolizumab with lenvatinib and chemotherapy in NSCLC patients with sensitizing EGFR, ALK, or ROS1 genetic aberration refractory to standard targeted therapy.
- Conditions
- Nsclc, EGFR Activating Mutation, EGF-R Positive Non-Small Cell Lung Cancer, ALK Gene Rearrangement Positive, ROS1 Gene Rearrangement, ROS1 Positive NSCLC - Reactive Oxygen Species 1 Positive Non-Small Cell Lung Cancer
- Being tested
- Pembrolizumab, Lenvatinib, Pemetrexed, Carboplatin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
200 mg Q3W
LenvatinibDrug
8 mg daily
PemetrexedDrug
500 mg/m2 Q3W
CarboplatinDrug
AUC5 Q3W
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Not described Receives: Drug: Pembrolizumab; Drug: Lenvatinib; Drug: Pemetrexed; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Proportion of patients who have a confirmed CR or PR per RECIST 1.1
Measured: 24 months
Secondary outcomes (3)
Progression-free survival
Time from randomization to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first
Measured: 24 months
Overall survival
Time from randomization to death from any cause or last follow-up date
Measured: 36 months
The incidence, severity as graded by NCI CTCAE v5.0, seriousness and relationship to study medication of adverse events (AEs)
Safety and tolerability
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2021
- Study start5 Oct 2021
- Primary completionAug 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NsclcStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr Joanne CHIU
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr Joanne CHIU, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04989322
- Sponsor's protocol ID
- 475-0708-MT-Lung
- Other IDs
- MK-3475-C50
- Status last verified
- Nov 2021
- First submitted
- 26 Jul 2021
- Last updated
- 8 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chan HW, Tse CCL, Li YC, Leung R, Kwok GW, Wong JSL, Li KH, Tsang JWY, Li CW, Lo JWY, Tang V, Hui R, Yau T, Ho JCM, Chiu JWY. A phase 2, open-label, single-arm study evaluating the combination of pembrolizumab, lenvatinib, carboplatin and pemetrexed in patients with metastatic non-small cell lung cancer harbouring targetable genomic alterations who progressed on standard tyrosine kinase inhibitors. Invest New Drugs. 2025 Dec;43(6):1191-1200. doi: 10.1007/s10637-025-01589-6. Epub 2025 Nov 10.
PubMed 41212380
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-label Single-arm Study to Evaluate the Combination of Pembrolizumab, Lenvatinib and Chemotherapy in Non-small Cell Lung Cancer (NSCLC) Harbouring Targetable Mutation and Failed Standard Tyrosine Kinase Inhibitors
- ClinicalTrials.gov ID
- NCT04989322
- Acronym / sponsor ID
- 475-0708-MT-Lung
- Conditions
- Nsclc, EGFR Activating Mutation, EGF-R Positive Non-Small Cell Lung Cancer, ALK Gene Rearrangement Positive, ROS1 Gene Rearrangement, ROS1 Positive NSCLC - Reactive Oxygen Species 1 Positive Non-Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Dr Joanne CHIUUniversity, hospital or other
- Study start
- 5 Oct 2021 (actual)
- Primary completion
- Aug 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 4 Aug 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.
Adding chemotherapy or anti-VEGF to immunotherapy is an emerging strategy to enhance the efficacy of immunotherapy in many cancers. This phase 2 study aims to explore the preliminary efficacy of combination pembrolizumab with lenvatinib and chemotherapy in NSCLC patients with sensitizing EGFR, ALK, or ROS1 genetic aberration refractory to standard targeted therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Pembrolizumab, Drug: Lenvatinib, Drug: Pemetrexed, Drug: Carboplatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Pembrolizumab200 mg Q3W | Drug | Treatment |
| Lenvatinib8 mg daily | Drug | Treatment |
| Pemetrexed500 mg/m2 Q3W | Drug | Treatment |
| CarboplatinAUC5 Q3W | Drug | Treatment |
Primary outcome
Overall response rate
Time frame: 24 months
Proportion of patients who have a confirmed CR or PR per RECIST 1.1
3 secondary outcomes
Progression-free survival
Time frame: 24 months
Overall survival
Time frame: 36 months
The incidence, severity as graded by NCI CTCAE v5.0, seriousness and relationship to study medication of adverse events (AEs)
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2021.
- Derived from this study: PubMed 41212380Chan HW, Tse CCL, Li YC, Leung R, Kwok GW, Wong JSL, Li KH, Tsang JWY, Li CW, Lo JWY, Tang V, Hui R, Yau T, Ho JCM, Chiu JWY. A phase 2, open-label, single-arm study evaluating the combination of pembrolizumab, lenvatinib, carboplatin and pemetrexed in patients with metastatic non-small cell lung cancer harbouring targetable genomic alterations who progressed on standard tyrosine kinase inhibitors. Invest New Drugs. 2025 Dec;43(6):1191-1200. doi: 10.1007/s10637-025-01589-6. Epub 2025 Nov 10.
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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.
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, Lenvatinib and Pemetrexed in people with Nsclc and EGFR Activating Mutation, run by Dr Joanne CHIU at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 8 Dec 2021. 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 Hong Kong. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr Joanne Chiu, MBBS (+852-22553111, jwychiu@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04989322, which also lists 1 linked publication.
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 8 Dec 2021.