Trial Title:
Evaluation of Programmed Death Ligand 1 (PDL1) Response to Treatment in Patient-derived Organoids and Immune-marker Positron Emission Tomography (PET) Scanning in Non-small Cell Lung Cancer (NSCLC)
NCT ID:
NCT06405230
Condition:
Lung Cancer, Non-Small Cell
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carboplatin
Pembrolizumab
Pemetrexed
Dostarlimab
Conditions: Keywords:
Non-small cell lung cancer
Pembrolizumab
Dostarlimab
Platinum-based chemotherapy doublet
Programmed death ligand 1
Positron emission tomography
Organoids
Artificial intelligence
Machine learning
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Pembrolizumab will be administered.
Arm group label:
Pembrolizumab ± Platinum-based chemotherapy doublet (PBCD)
Intervention type:
Biological
Intervention name:
Dostarlimab
Description:
Dostarlimab will be administered.
Arm group label:
Dostarlimab ± PBCD
Intervention type:
Drug
Intervention name:
Pemetrexed+ (carboplatin or cisplatin)
Description:
PBCD consisting of pemetrexed+ (carboplatin or cisplatin) will be administered.
Arm group label:
Dostarlimab ± PBCD
Arm group label:
Pembrolizumab ± Platinum-based chemotherapy doublet (PBCD)
Summary:
The goal of this clinical trial is to investigate the utility of two biomarker tools:
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.
Criteria for 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 available paired primary PDO (from the tumour resection at
time of diagnosis) that have been successfully established, passaged 5 times,
assessed by potassium chloride (KCL) biobank pathologist to be representative of
clinical tumour tissue sample, and characterized by multiomic analyses.
- Participants with known human immunodeficiency virus (HIV) infection are allowed
with the following requirements:
1. 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
2. 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/mm^3 during that time period)
3. 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
4. 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
5. No history of HIV-associated non-Hodgkin lymphoma ≤5 years prior to study entry
6. 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
Exclusion Criteria:
- Mixed lung carcinoma (small cell carcinoma and NSCLC), small cell carcinoma, large
cell neuroendocrine carcinoma, or sarcomatoid carcinoma histologies
- 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
- 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 Estimated glomerular filtration rate (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
Gender:
All
Minimum age:
30 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
GSK Investigational Site
Address:
City:
London
Zip:
SE1 9RT
Country:
United Kingdom
Contact:
Last name:
US GSK Clinical Trials Call Center
Phone:
877-379-3718
Email:
GSKClinicalSupportHD@gsk.com
Contact backup:
Last name:
EU GSK Clinical Trials Call Centre
Phone:
+44 (0) 20 8990 4466
Email:
GSKClinicalSupportHD@gsk.com
Investigator:
Last name:
Eleni Karapanagiotou
Email:
Principal Investigator
Start date:
August 15, 2024
Completion date:
July 2, 2027
Lead sponsor:
Agency:
GlaxoSmithKline
Agency class:
Industry
Source:
GlaxoSmithKline
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06405230
