NSCLC (Advanced Non-small Cell Lung Cancer)Phase 2NCT06951399
Tracking T-Cell Responses to Evaluate Pembrolizumab Effectiveness in Advanced Non-Small Cell Lung Cancer
A Phase 2 study testing Pembrolizumab (KEYTRUDA®) in people with NSCLC (Advanced Non-small Cell Lung Cancer) and NSCLC Stage IV Without EGFR/ALK Mutation, run by Rabin Medical Center at 1 site in Israel.
Trial summary
This study includes patients with advanced non-small cell lung cancer (NSCLC) - either unresectable stage III or stage IV adenocarcinoma without actionable driver mutations - who are treated with pembrolizumab in combination with platinum-based doublet chemotherapy, irrespective of PD-L1 expression levels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC (Advanced Non-small Cell Lung Cancer), NSCLC Stage IV Without EGFR/ALK Mutation, NSCLC Adenocarcinoma
- What is being tested?
- Pembrolizumab (KEYTRUDA®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Sep 2025to 30 Apr 2028
- 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
- Histologically confirmed diagnosis of NSCLC adenocarcinoma stage IV or unresectable stage III.
- Have measurable disease based on RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate organ function.
Who cannot join
- Aberration in one or more of molecular drivers.
- Has received prior systemic anti-cancer therapy prior to allocation.
- Known active CNS metastases and/or carcinomatous meningitis.
- Known additional malignancy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site
Davidoff Comprehensive Cancer Center, Rabin Medical Center
Petah Tikva, 4941492
Raphael, +972-3-9378000, arire@clalit.org.il
About this study
Official title: T-Cell Repertoire Sequencing: Assessing Pembrolizumab Efficacy in Advanced Non-Small Lung Cancer
This study includes patients with advanced non-small cell lung cancer (NSCLC) - either unresectable stage III or stage IV adenocarcinoma without actionable driver mutations - who are treated with pembrolizumab in combination with platinum-based doublet chemotherapy, irrespective of PD-L1 expression levels.
The primary objective is to assess treatment response through integration of serial T-cell receptor (TCR) repertoire sequencing (Rep-seq), capturing longitudinal changes in T-cell clonality and diversity. These immune dynamics will be correlated with radiographic response assessed by RECIST 1.1, with the aim of improving the accuracy of response classification, including differentiation between progression, pseudo-progression, and hyperprogression.
Additionally, circulating tumor DNA (ctDNA) levels will be measured longitudinally (pre-treatment and during treatment) to evaluate their potential as a complementary biomarker of disease burden and treatment efficacy in the context of chemo-immunotherapy.
- Conditions
- NSCLC (Advanced Non-small Cell Lung Cancer), NSCLC Stage IV Without EGFR/ALK Mutation, NSCLC Adenocarcinoma
- Being tested
- Pembrolizumab (KEYTRUDA®)
- Keywords
- metastatic NSCLC adenocarcinoma first-line pembrolizumab
- 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.
Pembrolizumab (KEYTRUDA®)Drug
IV Pembrolizumab 200 mg combined with pemetrexed and platinum (investigator's choice of cisplatin or carboplatin) every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab 200 mg combined with pemetrexed and platinum (cisplatin or carboplatin) | Experimental | Not described Receives: Drug: Pembrolizumab (KEYTRUDA®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in T-cell Receptor (TCR) Repertoire Clonality and Diversity Relative to Disease Response Assessed by RECIST v1.1
TCR sequencing will be performed on peripheral blood samples to assess clonality and diversity metrics. Changes in these metrics will be analyzed relative to clinical disease response evaluated according to RECIST version 1.1 criteria.
Measured: From date of randomization until the end of treatment, defined as a maximum of 35 cycles administered every 3 weeks (up to 2 years), or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2025
- Study start1 Sep 2025 (estimated)
- Primary completion30 Aug 2027 (estimated)
- Study completion30 Apr 2028 (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 NSCLC (Advanced Non-small Cell Lung Cancer)Studies 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- MSD Pharmaceuticals LLC
- Responsible party
- Principal investigator, ARI RAPHAEL, Rabin Medical Center
- Investigators
- Ari Raphael, Principal investigator, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06951399
- Sponsor's protocol ID
- 0026-25-RNC_MK3475-F34
- Status last verified
- Jul 2025
- First submitted
- 17 Apr 2025
- Last updated
- 22 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Disis ML. Immune regulation of cancer. J Clin Oncol. 2010 Oct 10;28(29):4531-8. doi: 10.1200/JCO.2009.27.2146. Epub 2010 Jun 1.
PubMed 20516428
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T-Cell Repertoire Sequencing: Assessing Pembrolizumab Efficacy in Advanced Non-Small Lung Cancer
- ClinicalTrials.gov ID
- NCT06951399
- Acronym / sponsor ID
- 0026-25-RNC_MK3475-F34
- Conditions
- NSCLC (Advanced Non-small Cell Lung Cancer), NSCLC Stage IV Without EGFR/ALK Mutation, NSCLC Adenocarcinoma
- Keywords
- metastatic NSCLC adenocarcinoma first-line pembrolizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Collaborators
- MSD Pharmaceuticals LLC
- Study start
- 1 Sep 2025 (estimated)
- Primary completion
- 30 Aug 2027 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 30 Apr 2025 (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 includes patients with advanced non-small cell lung cancer (NSCLC) - either unresectable stage III or stage IV adenocarcinoma without actionable driver mutations - who are treated with pembrolizumab in combination with platinum-based doublet chemotherapy, irrespective of PD-L1 expression levels.
The primary objective is to assess treatment response through integration of serial T-cell receptor (TCR) repertoire sequencing (Rep-seq), capturing longitudinal changes in T-cell clonality and diversity. These immune dynamics will be correlated with radiographic response assessed by RECIST 1.1, with the aim of improving the accuracy of response classification, including differentiation between progression, pseudo-progression, and hyperprogression.
Additionally, circulating tumor DNA (ctDNA) levels will be measured longitudinally (pre-treatment and during treatment) to evaluate their potential as a complementary biomarker of disease burden and treatment efficacy in the context of chemo-immunotherapy.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab 200 mg combined with pemetrexed and platinum (cisplatin or carboplatin) | Experimental | Drug: Pembrolizumab (KEYTRUDA®) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed diagnosis of NSCLC adenocarcinoma stage IV or unresectable stage III.
- Have measurable disease based on RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate organ function.
Key exclusion criteria (4 listed)
- Aberration in one or more of molecular drivers.
- Has received prior systemic anti-cancer therapy prior to allocation.
- Known active CNS metastases and/or carcinomatous meningitis.
- Known additional malignancy.
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 |
|---|---|---|
| Pembrolizumab (KEYTRUDA®)IV Pembrolizumab 200 mg combined with pemetrexed and platinum (investigator's choice of cisplatin or carboplatin) every 3 weeks | Drug | Pembrolizumab 200 mg combined with pemetrexed and platinum (cisplatin or carboplatin) |
Primary outcome
Change in T-cell Receptor (TCR) Repertoire Clonality and Diversity Relative to Disease Response Assessed by RECIST v1.1
Time frame: From date of randomization until the end of treatment, defined as a maximum of 35 cycles administered every 3 weeks (up to 2 years), or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first
TCR sequencing will be performed on peripheral blood samples to assess clonality and diversity metrics. Changes in these metrics will be analyzed relative to clinical disease response evaluated according to RECIST version 1.1 criteria.
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 22 Jul 2025.
- Background: PubMed 20516428Disis ML. Immune regulation of cancer. J Clin Oncol. 2010 Oct 10;28(29):4531-8. doi: 10.1200/JCO.2009.27.2146. Epub 2010 Jun 1.
- 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.
Ari Raphael principal investigator
Rabin Medical Center
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 (KEYTRUDA®) in people with NSCLC (Advanced Non-small Cell Lung Cancer) and NSCLC Stage IV Without EGFR/ALK Mutation, run by Rabin Medical Center at 1 site in Israel.
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 4 inclusion and 4 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 22 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 Israel. 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?
Contact Ari Raphael, M.D (+972-3-9378000, arire@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in T-cell Receptor (TCR) Repertoire Clonality and Diversity Relative to Disease Response Assessed by RECIST v1.1 (time frame: From date of randomization until the end of treatment, defined as a maximum of 35 cycles administered every 3 weeks (up to 2 years), or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first). 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 NCT06951399, 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 22 Jul 2025.