AzTrials
AzTrials

Lung Cancer, Non-Small CellPhase 1/2NCT06405230

Evaluation of Programmed Death Ligand 1 (PDL1) Response to Treatment in Extracellular Vesicles (EVs), Patient-derived Organoid (PDOs)s and Immune-marker Positron Emission Tomography (PET) Scanning in Non-small Cell Lung Cancer (NSCLC)

A Phase 1/2 study testing Pembrolizumab, Dostarlimab and Pemetrexed+ (carboplatin or cisplatin) in people with Lung Cancer, Non-Small Cell, run by GlaxoSmithKline at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The goal of this clinical trial is to investigate the utility of biomarker tools Extracellular Vesicles (EVs), Patient-derived organoid (PDOs), and PDL1 PET imaging for predicting how participants with recurrent NSCLC respond to standard of care treatment in the advanced/metastatic stages. Read more about this study

Who is it for?
Ages 30 years and older
Conditions the study is for
Lung Cancer, Non-Small Cell
What is being tested?
Pembrolizumab, Dostarlimab and Pemetrexed+ (carboplatin or cisplatin)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited Kingdom
Study dates
10 Oct 2025to 13 Jul 2026
Phase
Phase 1/2
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 30 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have histologically- or cytologically documented NSCLC who present with recurrent advanced or metastatic disease after initial diagnosis of Stage 1-3 lung cancer
  • Participants must have been initially diagnosed with operable Stage 1-3 NSCLC and received curative resection ± (neo) adjuvant treatment
  • Identifiable PDL1 status prior to randomisation
  • Participants must have biopsy-confirmed recurrence of their initial NSCLC with advanced/metastatic presentation
  • Has at least 1 measurable (target) lesion per Response Evaluation Criteria in Solid Tumours (RECIST) version (v) 1.1 by Computed tomography (CT) or magnetic resonance imaging (MRI). Measurable lesions that have been previously irradiated are not considered measurable and cannot be target lesions
  • Participants must be deemed by investigator to be appropriate to receive 1L systemic therapy (i.e., anti-PD1 ± PBCD)
Show all 17Show fewer
  • Participants must have had tissue submitted for attempted PDO generation. (Note: patients deemed to have successfully established paired 1o PDO [from the tumour resection at time of diagnosis]are those whose PDO cultures have been passaged 2 times, with a reasonable proliferation rate. This designation can be made prior to or during trial participation. A KCL biobank pathologist will confirm the PDO's representation of clinical tumour tissue sample at the time of multiomic analysis).
  • Participants with known human immunodeficiency virus (HIV) infection are allowed with the following requirements:
  • Documented evidence of plasma HIV-1 ribonucleic acid (RNA) persistently <50 copies per millilitre (c/mL) ≤3 months prior to and at Screening. In the >3 to 12 months prior to Screening, plasma HIV-1 RNA consistently <50 c/mL required; if single increases ≥50 c/mL occurred, they cannot have been persistent nor associated with antiretroviral resistance per investigator assessment
  • cluster of differentiation 4 (CD4) cell count >350 cells per cubic millimetre (cells/mm^3) over past 12 months and at Screening (and no measurement ≤350 cells/mm3 during that time period)
  • Must be on an uninterrupted combination antiretroviral therapy regimen for at least 3 months prior to Screening, with combination antiretroviral therapy regimen consistent with locally recommended guidelines
  • Participants with history of Centres for Disease Control and Prevention (CDC) Stage 3 acquired immunodeficiency syndrome (AIDS)-defining disease are allowed if AIDS-defining disease has been treated and cured or is stable for ≥3 months prior to study entry. Cutaneous Kaposi's sarcoma not requiring systemic therapy is allowed
  • No history of HIV-associated non-Hodgkin lymphoma ≤5 years prior to study entry
  • No treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
  • Fresh tumour biopsy (taken as part of disease recurrence evaluation) is a requirement, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk. If fresh biopsy sample is not available, an archival sample may be used
  • Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2
  • Has adequate organ function per the investigator

Who cannot join

  • Mixed lung carcinoma (small cell carcinoma and NSCLC), small cell carcinoma, large cell neuroendocrine carcinoma, sarcomatoid carcinoma, or any other histologies that would not benefit from anti-PD1 ± PBCD. If a potential participant has histology other than squamous cell or adenocarcinoma (e.g., mixed histology that is predominantly NSCLC, large cell without neuroendocrine features) but is deemed appropriate for treatment with anti-PD1 ± PBCD, they may be eligible pending discussion with the sponsor.
  • For participants who received adjuvant therapy that included anti-PD(L)1 Checkpoint inhibitor (CPI) following surgical resection, their last dose of anti-PD(L)1 was <6 months from the date of first 89Zr-durvalumab-PET tracer injection
  • Participant has known central nervous system (CNS) metastases and/or carcinomatous meningitis that per investigator puts the participant at prohibitive risk to enrol in study
  • Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Participant with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with assessments of the study may be included only after discussion with the Medical Monitor
  • Participant is considered a poor medical risk by the investigator due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled chronic obstructive pulmonary disease; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent)
  • Participant is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment
Show all 22Show fewer
  • Participant has a diagnosed immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy that per investigator puts the participant at prohibitive risk to enrol in the study
  • Participant has an active HIV infection that per investigator puts the participant at prohibitive risk to enrol in study
  • Participant has tested positive for the presence of hepatitis B surface antigen and/or Hepatitis B virus (HBV) core antibody or has a positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of anti-cancer treatment
  • Participant has an active autoimmune disease that has required systemic treatment (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy up to 5 milligrams (mg) prednisone or equivalent for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Use of inhaled steroids, topical steroids, local injection of steroids, and steroid eye drops are allowed
  • Participant has history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan that per investigator and medical monitor puts the participant at prohibitive risk to enrol in study
  • Participant is currently participating and receiving study therapy or has participated in a study of an investigational agent and received investigational therapy or used an investigational device within 4 weeks prior to the first dose of study drug
  • Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal/gastric varices, or persistent jaundice
  • Participant has not recovered adequately (≤ Grade 1) per investigator from AEs and/or complications from any major surgery prior to starting therapy
  • Participant has received a vaccine other than a vaccine against Severe acute respiratory syndrome coronavirus disease 19 (SARS-CoV-2) infection (COVID-19) within 7 days of planned start of study therapy. The use of all COVID-19 vaccines is allowed, with the exception of COVID-19 vaccines using the recombinant adenoviral vector platform within 30 days of planned start of study therapy. If a COVID-19 vaccine using this platform is to be administered within 30 days of planned start of study therapy, this must first be discussed with and approved by the sponsor's medical monitor
  • Participant has received any form of anti-cancer therapy (e.g., chemotherapy, radiation, immunotherapy) for lung cancer recurrence after initial surgery
  • Is receiving any additional anticancer post-surgery±(neo) adjuvant therapy or experimental therapy. No other experimental therapies (including but not limited to chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, or other experimental drugs) of any kind are permitted while the participant is receiving study intervention
  • NSCLC with known sensitizing EGFR mutations, Anaplastic lymphoma kinase (ALK) translocations, or c-ros oncogene 1 (ROS1) mutations from resected tissue at the time of initially surgery and/or tissue biopsy at the time of screening
  • Has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or known allergies to pembrolizumab, dostarlimab, durvalumab, or their excipients
  • Symptomatic herpes zoster within 3 months prior to screening
  • Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and TB testing: either a positive Tuberculin skin test (TST) (defined as a skin induration ≥5 millimetres [mm] at 48 to 72 hours, regardless of Bacillus Calmette-Guerin or other vaccination history) or a positive (not indeterminate) TB test such as QuantiFERON-TB Gold Plus test
  • QT interval corrected for heart rate according to Fridericia's formula (QTc) >450 milliseconds (msec) or QTc >480 msec in participants with bundle branch block

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    London, SE1 9RT

Other trials in United Kingdom

About this study

Official title: A Pilot/Exploratory Translational Study to Evaluate Response to Dostarlimab and Pembrolizumab in Extracellular Vesicles (EVs) or Patient-derived Organoids (PDOs) and by Zirconium-89 Labelled Programmed Death Ligand 1 Positron Emission Tomography in Participants With Recurrent Non-small Cell Lung Cancer

The goal of this clinical trial is to investigate the utility of biomarker tools Extracellular Vesicles (EVs), Patient-derived organoid (PDOs), and PDL1 PET imaging for predicting how participants with recurrent NSCLC respond to standard of care treatment in the advanced/metastatic stages.

Being tested
Pembrolizumab, Dostarlimab, Pemetrexed+ (carboplatin or cisplatin)
Keywords
Non-small cell lung cancer, Pembrolizumab, Dostarlimab, Platinum-based chemotherapy doublet, Programmed death ligand 1, Positron emission tomography, Extracellular Vesicles, Organoids, Artificial intelligence, Machine learning
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.

  • PembrolizumabBiological

    Pembrolizumab will be administered.

  • DostarlimabBiological

    Dostarlimab will be administered.

  • Pemetrexed+ (carboplatin or cisplatin)Drug

    PBCD consisting of pemetrexed+ (carboplatin or cisplatin) will be administered.

Study groups in NCT06405230
Study groupRoleWhat they receive
Pembrolizumab ± Platinum-based chemotherapy doublet (PBCD)ExperimentalParticipants will receive pembrolizumab with or without PBCD.
Receives: Biological: Pembrolizumab; Drug: Pemetrexed+ (carboplatin or cisplatin)
Dostarlimab ± PBCDExperimentalParticipants will receive dostarlimab with or without PBCD.
Receives: Biological: Dostarlimab; Drug: Pemetrexed+ (carboplatin or cisplatin)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Spearman's rank correlation coefficient between treatment-induced PDL1 modulation in, 1o PDOs and/or extracellular vesicles (EVs) and PET after treatment

    The primary endpoint is the correlation between "treatment-induced change in PDL1 in PDOs which will be evaluated as the ratio of PDL1 positive cells before and after treatment using flow cytometry and multiplex immunofluorescence analysis" AND/OR "treatment-induced change in PDL1 in EVs which will be evaluated as the ratio of PDL1 positive cells before and after treatment using flow cytometry and multiplex immunofluorescence analysis" and "changes in PET which will be evaluated as the percentage difference in PDL1-PET standard uptake volume (SUV) uptake in lesions from the baseline to on-treatment" using the formula for Spearman's rank correlation coefficient. The Spearmans rank correlation coefficient can take values from +1 to -1 where a value of +1 indicates a perfect positive association, a value of 0 indicates no association and a value of -1 indicates a perfect negative association.

    Measured: Up to approximately 9 months

Secondary outcomes (7)

  1. Spearman's rank correlation coefficient between treatment-induced PDL1 modulation in 1o PDOs and tumour response to anti- Programmed death 1 (PD1) based first line (1L) advanced/metastatic NSCLC treatment

    The secondary endpoint is the correlation between "treatment-induced change in PDL1 in PDOs which will be evaluated as the ratio of PDL1 positive cells before and after treatment using flow cytometry and multiplex immunofluorescence analysis" AND "tumor response rate which will be assessed based on RECIST v1.1 per investigator assessment" using the formula for Spearman's rank correlation coefficient. The Spearmans rank correlation coefficient can take values from +1 to -1 where a value of +1 indicates a perfect positive association, a value of 0 indicates no association and a value of -1 indicates a perfect negative association.

    Measured: Up to approximately 9 months

  2. Spearman's rank correlation coefficient between treatment-induced PDL1 modulation in EVs and tumour response to anti- Programmed death 1 (PD1) based first line (1L) advanced/metastatic NSCLC treatment

    The secondary endpoint is the correlation between "treatment-induced change in PDL1 in EVs which will be evaluated as the ratio of PDL1 positive cells before and after treatment using flow cytometry and multiplex immunofluorescence analysis" AND "tumor response rate which will be assessed based on RECIST v1.1 per investigator assessment" using the formula for Spearman's rank correlation coefficient. The Spearmans rank correlation coefficient can take values from +1 to -1 where a value of +1 indicates a perfect positive association, a value of 0 indicates no association and a value of -1 indicates a perfect negative association.

    Measured: Up to approximately 9 months

  3. Spearman's rank correlation coefficient between treatment-induced PDL1 modulation by PET and radiological tumour response to anti-PD1 based 1L advanced/metastatic NSCLC treatment

    The secondary endpoint is the correlation between "changes in PET which will be evaluated as the percentage difference in PDL1-PET standard uptake volume (SUV) uptake in lesions from the baseline to on-treatment" AND "tumor response rate which will be assessed based on RECIST v1.1 per investigator assessment" using the formula for Spearman's rank correlation coefficient. The Spearmans rank correlation coefficient can take values from +1 to -1 where a value of +1 indicates a perfect positive association, a value of 0 indicates no association and a value of -1 indicates a perfect negative association.

    Measured: Up to approximately 9 months

  4. Number of participants with adverse events (AEs) and serious adverse events (SAEs) following Zirconium-89 (89Zr-durvalumab)-PET radiotracer injection

    Measured: Up to Week 4

  5. Number of participants with treatment emergent AEs (TEAEs), immune-related AEs, and SAEs by severity

    Measured: Up to approximately 9 months

  6. Number of participants with TEAEs or SAEs, leading to dose delays, withdrawals, or death

    Measured: Up to approximately 9 months

  7. Number of participants with clinically significant changes in laboratory, vital signs, and safety assessment parameters

    Measured: Up to approximately 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2024
  2. Study start10 Oct 2025
  3. Primary completion13 Jul 2026
  4. Study completion13 Jul 2026

Why it stopped: Operational challenges

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06405230
Sponsor's protocol ID
221861
Status last verified
Aug 2026
First submitted
18 Apr 2024
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab, Dostarlimab and Pemetrexed+ (carboplatin or cisplatin) in people with Lung Cancer, Non-Small Cell, run by GlaxoSmithKline at 1 site in United Kingdom.

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 17 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: stopped early, as of the sponsor's last update on 3 Sep 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 United Kingdom. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was stopped early (reason given: Operational challenges). Results are not available in the source record.

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?

Spearman's rank correlation coefficient between treatment-induced PDL1 modulation in, 1o PDOs and/or extracellular vesicles (EVs) and PET after treatment (time frame: Up to approximately 9 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 NCT06405230.

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 3 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in