Clinical Trials/NCT06405230

NCT06405230

Recruiting

Phase 1

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

GlaxoSmithKline1 site in 1 country40 target enrollmentDecember 30, 2025

ConditionsLung Cancer, Non-Small Cell

InterventionsPembrolizumab Pemetrexed+ (carboplatin or cisplatin)Dostarlimab

DrugsPembrolizumab Pemetrexed+ (carboplatin or cisplatin)

Overview

Phase: Phase 1
Intervention: Pembrolizumab
Conditions: Lung Cancer, Non-Small Cell
Sponsor: GlaxoSmithKline
Enrollment: 40
Locations: 1
Primary Endpoint: Spearman's rank correlation coefficient between treatment-induced PDL1 modulation in, 1o PDOs and/or extracellular vesicles (EVs) and PET after treatment
Status: Recruiting
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

December 30, 2025

End Date

October 10, 2029

Last Updated

2 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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)
•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)

Exclusion Criteria

•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
•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

Arms & Interventions

Pembrolizumab ± Platinum-based chemotherapy doublet (PBCD)

Participants will receive pembrolizumab with or without PBCD.

Intervention: Pembrolizumab

Pembrolizumab ± Platinum-based chemotherapy doublet (PBCD)

Participants will receive pembrolizumab with or without PBCD.

Intervention: Pemetrexed+ (carboplatin or cisplatin)

Dostarlimab ± PBCD

Participants will receive dostarlimab with or without PBCD.

Intervention: Dostarlimab

Dostarlimab ± PBCD

Participants will receive dostarlimab with or without PBCD.

Intervention: Pemetrexed+ (carboplatin or cisplatin)

Outcomes

Primary Outcomes

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 29 months

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.

Secondary Outcomes

Number of participants with adverse events (AEs) and serious adverse events (SAEs) following Zirconium-89 (89Zr-durvalumab)-PET radiotracer injection(Up to Week 4)
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(Up to approximately 34.5 months)
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(Up to approximately 34.5 months)
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(Up to approximately 34.5 months)
Number of participants with treatment emergent AEs (TEAEs), immune-related AEs, and SAEs by severity(Up to approximately 34.5 months)
Number of participants with TEAEs or SAEs, leading to dose delays, withdrawals, or death(Up to approximately 34.5 months)
Number of participants with clinically significant changes in laboratory, vital signs, and safety assessment parameters(Up to approximately 34.5 months)