Non-small Cell Lung Cancer MetastaticPhase 3High FiveNCT07715396
Addition of Platinum-based Chemotherapy to Tislelizumab in PD-L1high Metastatic Non-small Cell Lung Cancer With a High Tumor Burden
A Phase 3 study testing Tislelizumab, Tislelizumab Combined With Chemotherapy and Pembrolizumab in people with Non-small Cell Lung Cancer Metastatic, run by AIO-Studien-gGmbH at 1 site in Germany.
Trial summary
AIO-TRK/YMO-0425 (High Five) is a phase III, open-label randomized-controlled, multicenter study to evaluate the progression-free survival by the addition of platinum-based chemotherapy to immunotherapy (IO) compared to IO monotherapy in patients with PD-L1high mNSCLC featuring a high tumor burden. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Metastatic
- What is being tested?
- Tislelizumab, Tislelizumab Combined With Chemotherapy and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 1 siteGermany
- Study dates
- 30 Oct 2026to 30 Oct 2031
- Phase
- Phase 3
- 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
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study
- Histologically confirmed and treatment-naïve non-small cell lung cancer UICC 9th stage IV
- PD-L1 ≥ 50%
- High Tumor Burden defined as the longest diameter of the tumor or at least one metastasis ≥ 50mm and no eligibility for a curative treatment approach
- Measurable disease according to RECIST v1.1
- No actionable genomic alterations (AGA) qualifying for targeted first-line treatment
Show all 13Show fewer
- Eligible for platinum-based chemoimmunotherapy
- Age ≥18 years
- Patients with brain metastases may be included, except when whole brain radiation therapy (WBRT) is pending. In such case, patients may be included 7 or more days after completion of WBRT.
- Female subjects of childbearing potential (FOCBP) should be using highly effective contraceptive measures and must have a negative urine or serum pregnancy test within 7 days prior to start of study treatment and must not be breast-feeding prior to start of trial. Non-child-bearing potential must be evidenced by fulfilling one of the following criteria at screening:
- Postmenopausal, defined as at least 12 months with no menses without an alternative medical cause; a follicle stimulating hormone (FSH) level in the postmenopausal range for the institution may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
- have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, at least 6 weeks prior to screening (Women with tubal ligation are still considered of child-bearing potential according to CTFG Guidance).
- have a congenital or acquired condition that prevents childbearing Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Who cannot join
- Presence of a condition, disease or abnormality that in the opinion of the Investigator would compromise the safety of the patient, the patient's ability to comply with the study procedures (e.g., dementia) or the quality of the data. Specifically, the presence of any preexisting autoimmune disease that prohibits dosing of IMP as per treatment modification guidelines in the current IB/SmPC
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study
- Concurrent malignancy other than NSCLC requiring active treatment
- Has known hypersensitivity to the IMPs or to any component of the planned regimen, their metabolites, or formulation excipients, or any other contraindication to any component of the planned study regimen according to the tislelizumab IB and the relevant SmPCs
- Current use of systemic corticosteroids that exceed 10 mg/day of prednisone or is equivalent medication within 3 days before the first dose of tislelizumab/pembrolizumab, except the following criterion:
- steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
Show all 10Show fewer
- Concurrent yellow fever vaccination
- Female subjects who are pregnant or breast-feeding or patients of reproductive potential who are not employing a highly effective method of birth control (failure rate of less than 1% per year)
- Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities
- Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site
University of Frankfurt
Frankfurt
Sophie Ambrosius, +49 69 6301 5677, s.ambrosius@med.uni-frankfurt.de
Sophie Ambrosius
About this study
AIO-TRK/YMO-0425 (High Five) is a phase III, open-label randomized-controlled, multicenter study to evaluate the progression-free survival by the addition of platinum-based chemotherapy to immunotherapy (IO) compared to IO monotherapy in patients with PD-L1high mNSCLC featuring a high tumor burden.
Read the detailed description
This is a randomized, open-label, multicenter, phase III trial. Patients with squamous or non-squamous non-small-cell lung cancer (NSCLC) UICC 9th Stage IV, a high PD-L1 expression level (PD-L1 ≥ 50%) and a high tumor burden (baseline tumor size (BTS) ≥ 50 mm), eligible for 1st-line treatment with platinum and immunotherapy, will be enrolled in this trial. The patients will receive immuno-monotherapy (tislelizumab or pembrolizumab) or immunotherapy plus platinum-based doublet chemotherapy (squamous NSCLC: tislelizumab + carboplatin + (nab-) paclitaxel with tislelizumab maintenance; non-squamous NSCLC: tislelizumab + cis-/carboplatin + pemetrexed with tislelizumab maintenance) for a maximum of 24 months, with a subsequent follow-up phase until end of study (26 months after last patient in or until all patients have finished a 90-days safety follow-up) or preliminary termination or death. Standard of care tumor assessments will be performed and recorded according to RECIST version 1.1., at baseline/screening, throughout the treatment phase (initially after 6 weeks, thereafter each 12 ± 2 weeks), at end of treatment and during follow up.
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Being tested
- Tislelizumab, Tislelizumab Combined With Chemotherapy, Pembrolizumab
- Keywords
- Metastatic, Stage IV, NSCLC, High tumor burden, Immunotherapy, Platinum-based chemotherapy
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
Tislelizumab monotherapy 200 mg i.v. q3w
Tislelizumab Combined With ChemotherapyDrug
Non-squamous NSCLC: tislelizumab 200 mg i.v. + platinum-based chemotherapy (cisplatin 75 mg/m2 i.v. or carboplatin AUC 5-6 i.v.) + pemetrexed 500 mg/m2 i.v.; squamous NSCLC: tislelizumab 200 mg i.v. + carboplatin AUC 5-6 i.v. + (nab)paclitaxel (nab-paclitaxel 100 mg/m2 i.v., paclitaxel 175 or 200 mg/m2 i.v.
PembrolizumabDrug
Pembrolizumab monotherapy 200 mg i.v. q3w
| Study group | Role | What they receive |
|---|---|---|
| Immune-monotherapy | Active comparator | Tislelizumab monotherapy 200 mg i.v. q3w or pembrolizumab monotherapy 200 mg i.v. q3w or Receives: Drug: Tislelizumab; Drug: Pembrolizumab |
| Tislelizumab + platinum-based doublet chemotherapy | Experimental | Non-squamous NSCLC: tislelizumab 200 mg i.v. + platinum-based chemotherapy (cisplatin 75 mg/m2 i.v. or carboplatin AUC 5-6 i.v.) + pemetrexed 500 mg/m2 i.v.; squamous NSCLC: tislelizumab 200 mg i.v. + carboplatin AUC 5-6 i.v. + (nab)paclitaxel (nab-paclitaxel 100 mg/m2 i.v., paclitaxel 175 or 200 mg/m2 i.v. Receives: Drug: Tislelizumab Combined With Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
time from randomization to the date of first objective disease progression (according to RECIST V1.1 as determined by blinded independent central review [BICR]) or death of any cause, whichever occurs first
Measured: max. 50 months
Secondary outcomes (6)
Overall survival
Measured: max. 50 months
Objective response rate
rate of patients with complete response (CR) or partial response (PR) as best response, based on assessment according to RECIST1.1 by local investigator, as well as by BICR
Measured: max. 50 months
Duration of response
time from first occurrence of CR or PR as best response to the date of first objective disease progression (according to RECIST V1.1 by local investigator, as well as by BICR) or death of any cause, whichever occurs first
Measured: max. 50 months
Disease control rate
rate of patients with CR, PR or stable disease (SD) as best response, based on assessment according to RECIST1.1 by local investigator, as well as by BICR
Measured: max. 50 months
Progression-free survival according to RECIST V1.1 as determined by local investigator
time from randomization to the date of first objective disease progression (according to RECIST V1.1 as determined by local investigator) or death of any cause, whichever occurs first
Measured: max. 50 months
Quality of life (FACT-L)
Functional Assessment of Cancer Therapy-Lung Total score 0-136; higher scores indicate better quality of life
Measured: max. 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2026
- Study start30 Oct 2026 (estimated)
- Primary completion30 Oct 2031 (estimated)
- Study completion30 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer MetastaticStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AIO-Studien-gGmbH
- Sponsor type
- University, hospital or other
- Collaborators
- BeOne Medicines
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07715396
- Sponsor's protocol ID
- AIO-TRK/YMO-0425
- Other IDs
- 2026-525497-18-00
- Acronym
- High Five
- Status last verified
- Oct 2026
- First submitted
- 15 Jul 2026
- Last updated
- 26 Oct 2026
- 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 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Addition of Platinum-based Chemotherapy to Tislelizumab in PD-L1high Metastatic Non-small Cell Lung Cancer With a High Tumor Burden
- ClinicalTrials.gov ID
- NCT07715396
- Acronym / sponsor ID
- High Five / AIO-TRK/YMO-0425
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Keywords
- Metastatic, Stage IV, NSCLC, High tumor burden, Immunotherapy, Platinum-based chemotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- AIO-Studien-gGmbHUniversity, hospital or other
- Collaborators
- BeOne Medicines
- Study start
- 30 Oct 2026 (estimated)
- Primary completion
- 30 Oct 2031 (estimated)
- Study completion
- 30 Oct 2031 (estimated)
- First posted
- 20 Jul 2026 (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.
AIO-TRK/YMO-0425 (High Five) is a phase III, open-label randomized-controlled, multicenter study to evaluate the progression-free survival by the addition of platinum-based chemotherapy to immunotherapy (IO) compared to IO monotherapy in patients with PD-L1high mNSCLC featuring a high tumor burden.
Detailed description
This is a randomized, open-label, multicenter, phase III trial. Patients with squamous or non-squamous non-small-cell lung cancer (NSCLC) UICC 9th Stage IV, a high PD-L1 expression level (PD-L1 ≥ 50%) and a high tumor burden (baseline tumor size (BTS) ≥ 50 mm), eligible for 1st-line treatment with platinum and immunotherapy, will be enrolled in this trial. The patients will receive immuno-monotherapy (tislelizumab or pembrolizumab) or immunotherapy plus platinum-based doublet chemotherapy (squamous NSCLC: tislelizumab + carboplatin + (nab-) paclitaxel with tislelizumab maintenance; non-squamous NSCLC: tislelizumab + cis-/carboplatin + pemetrexed with tislelizumab maintenance) for a maximum of 24 months, with a subsequent follow-up phase until end of study (26 months after last patient in or until all patients have finished a 90-days safety follow-up) or preliminary termination or death. Standard of care tumor assessments will be performed and recorded according to RECIST version 1.1., at baseline/screening, throughout the treatment phase (initially after 6 weeks, thereafter each 12 ± 2 weeks), at end of treatment and during follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immune-monotherapy | Active comparator | Drug: Tislelizumab, Drug: PembrolizumabTislelizumab monotherapy 200 mg i.v. q3w or pembrolizumab monotherapy 200 mg i.v. q3w or |
| Tislelizumab + platinum-based doublet chemotherapy | Experimental | Drug: Tislelizumab Combined With ChemotherapyNon-squamous NSCLC: tislelizumab 200 mg i.v. + platinum-based chemotherapy (cisplatin 75 mg/m2 i.v. or carboplatin AUC 5-6 i.v.) + pemetrexed 500 mg/m2 i.v.; squamous NSCLC: tislelizumab 200 mg i.v. + carboplatin AUC 5-6 i.v. + (nab)paclitaxel (nab-paclitaxel 100 mg/m2 i.v., paclitaxel 175 or 200 mg/m2 i.v. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study
- Histologically confirmed and treatment-naïve non-small cell lung cancer UICC 9th stage IV
- PD-L1 ≥ 50%
- High Tumor Burden defined as the longest diameter of the tumor or at least one metastasis ≥ 50mm and no eligibility for a curative treatment approach
- Measurable disease according to RECIST v1.1
Key exclusion criteria (10 listed)
- Presence of a condition, disease or abnormality that in the opinion of the Investigator would compromise the safety of the patient, the patient's ability to comply with the study procedures (e.g., dementia) or the quality of the data. Specifically, the presence of any preexisting autoimmune disease that prohibits dosing of IMP as per treatment modification guidelines in the current IB/SmPC
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study
- Concurrent malignancy other than NSCLC requiring active treatment
- Has known hypersensitivity to the IMPs or to any component of the planned regimen, their metabolites, or formulation excipients, or any other contraindication to any component of the planned study regimen according to the tislelizumab IB and the relevant SmPCs
- Current use of systemic corticosteroids that exceed 10 mg/day of prednisone or is equivalent medication within 3 days before the first dose of tislelizumab/pembrolizumab, except the following criterion:
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 |
|---|---|---|
| TislelizumabTislelizumab monotherapy 200 mg i.v. q3w | Drug | Immune-monotherapy |
| Tislelizumab Combined With ChemotherapyNon-squamous NSCLC: tislelizumab 200 mg i.v. + platinum-based chemotherapy (cisplatin 75 mg/m2 i.v. or carboplatin AUC 5-6 i.v.) + pemetrexed 500 mg/m2 i.v.; squamous NSCLC: tislelizumab 200 mg i.v. + carboplatin AUC 5-6 i.v. + (nab)paclitaxel (nab-paclitaxel 100 mg/m2 i.v., paclitaxel 175 or 200 mg/m2 i.v. | Drug | Tislelizumab + platinum-based doublet chemotherapy |
| PembrolizumabPembrolizumab monotherapy 200 mg i.v. q3w | Drug | Immune-monotherapy |
Primary outcome
Progression-free survival
Time frame: max. 50 months
time from randomization to the date of first objective disease progression (according to RECIST V1.1 as determined by blinded independent central review [BICR]) or death of any cause, whichever occurs first
6 secondary outcomes
Overall survival
Time frame: max. 50 months
Objective response rate
Time frame: max. 50 months
Duration of response
Time frame: max. 50 months
Disease control rate
Time frame: max. 50 months
Progression-free survival according to RECIST V1.1 as determined by local investigator
Time frame: max. 50 months
Quality of life (FACT-L)
Time frame: max. 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 26 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Non-small Cell Lung Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 3
Study of Daraxonrasib (RMC-6236) in Patients With RAS Mutated NSCLC (RASolve 301)
NSCLC (Non-small Cell Lung Cancer), Non-Small Cell Lung Cancer
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tislelizumab, Tislelizumab Combined With Chemotherapy and Pembrolizumab in people with Non-small Cell Lung Cancer Metastatic, run by AIO-Studien-gGmbH at 1 site in Germany.
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 13 inclusion and 10 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 26 Oct 2026. 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 Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Gordana Bothe (+4930814534443, gordana.bothe@aio-studien-ggmbh.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: max. 50 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 26 Oct 2026.