A Phase 2, Randomized, Open-label, Platform Study Utilizing a Master Protocol to Evaluate Novel Immunotherapy Combinations in Participants with Previously Untreated, Locally Advanced/Metastatic, Programmed Death Ligand 1-Selected Non Small Cell Lung Cancer
- Conditions
- lung cancerNSCLC10029107
- Registration Number
- NL-OMON51766
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
Participants are eligible to be included in the study only if all of the
following criteria apply.
1. Is capable of giving signed informed consent as described in Section 11.6 of
the protocol, which includes compliance with the requirements and restrictions
listed in the ICF and in this protocol.
2. Is, at the time of signing the ICF, at least 18 years old or the legal age
of consent in the jurisdiction in which the study is taking place.
3. Has a histologically or cytologically confirmed diagnosis of locally
advanced unresectable NSCLC not eligible for curative surgery and/or definitive
radiotherapy with or without chemotherapy or metastatic NSCLC (squamous or
nonsquamous). Mixed tumors will be categorized by the predominant cell type; if
small-cell or neuroendocrine elements are present, the participant is
ineligible.
4. Has not received prior systemic therapy for their locally advanced or
metastatic NSCLC.
NOTE: Completion of treatment with cytotoxic chemotherapy and/or radiation as
part of neoadjuvant/adjuvant therapy is allowed if therapy was completed at
least 6 months prior to the diagnosis of locally advanced or metastatic
disease. Prior treatment with neoadjuvant/adjuvant immunotherapy is not
permitted.
5. Provides a tumor tissue sample obtained at the time of or after the initial
diagnosis of locally advanced or metastatic NSCLC. Although a fresh tumor
tissue sample obtained during screening is preferred, an archival tumor
specimen (collected within 2 years prior to screening*) is acceptable. Tumor
tissue must be from a site not previously irradiated. Biopsies obtained prior
to the administration of any systemic therapy administered for the treatment of
a participant*s tumor (such as neoadjuvant/adjuvant therapy) are not
acceptable. Needle or excisional biopsies or resected tissue is required.
Cytological specimens such as fine needle aspirates, bone marrow samples, or
cell blocks are not acceptable, nor are bone specimens.
*NOTE: If multiple specimens are available, the most recent archival tumor
specimen should be submitted.
6. Has a PD-L1-high (TC/TPS *50%) tumor as determined by the DAKO 22C3 or
VENTANA SP263 assay performed by a local laboratory or by the VENTANA SP263
assay at a central laboratory.
NOTE: Other assays for PD-L1 expression levels will not be accepted to
determine eligibility. Local laboratory testing for PD-L1 status must be
performed on tumor tissue samples meeting the requirements specified in
Inclusion Criterion 5.
7. Has measurable disease based on RECIST 1.1 (Appendix 7 of the protocol), as
determined by the investigator.
8. Has an ECOG PS (Appendix 1 of the protocol) of 0 or 1.
9. Has adequate organ function, as defined in Table 1 of the protocol.
10. If of childbearing potential, female participants must be willing to use
adequate contraception. Contraceptive use by female participants should be
consistent with local regulations regarding the methods of contraception for
those participating in clinical studies.
• A female participant is eligible to participate if she is not pregnant or
breastfeeding, and 1 of the following conditions applies:
- Is a woman of non-childbearing potential as defined in Appendix 3 of the
protocol.
or
- Is a woman of childbearing potential
Participants are excluded from the study if any of the following criteria apply.
1. Has NSCLC with a tumor that harbors any of the following molecular
alterations:
a. EGFR mutations that are sensitive to available targeted inhibitor therapy
(including, but not limited to, deletions in exon 19, exon 20 insertion
mutation, and exon 21 [L858R] substitution mutation). All participants with
nonsquamous histology must have been tested for EGFR mutation status using a
tissue-based test; use of an approved test is strongly encouraged. Participants
with squamous histology do not need to be tested for EGFR mutation status.
Participants with nonsquamous histology and unknown or indeterminate EGFR
status are excluded.
b. ALK translocations that are sensitive to available targeted inhibitor
therapy. All participants with nonsquamous histology must have been tested for
ALK fusion mutation status using a tissue-based test; use of an approved test
is strongly encouraged. Participants with squamous histology do not need to be
tested for ALK mutation status. Participants with nonsquamous histology and
with unknown or indeterminate ALK status are excluded.
c. Any other known genomic aberrations or oncogenic driver mutations for which
a locally approved targeted therapy is available for first-line treatment of
locally advanced or metastatic NSCLC.
2. Has had major surgery within 4 weeks of the first dose of study intervention
or has received lung radiation therapy of >30 Gy (for any purpose, including
palliatively) within 6 months prior to the first dose of study intervention.
3. Has received prior therapy with any immune-checkpoint inhibitors, including
antibodies or drugs targeting PD-1, PD-L1, CTLA-4, TIGIT, CD96, or other
checkpoint pathways.
4. Has never smoked, defined as smoking <100 tobacco cigarettes in a lifetime.
5. Has an invasive malignancy or history of invasive malignancy other than the
disease under study within the last 5 years, except as noted below:
a. Participants may be enrolled in the study with a history of any other
invasive malignancy for which the participant was definitively treated, from
which the participant has been disease-free for at least 2 years, and which, in
the opinion of the principal investigator and sponsor/medical monitor, is not
expected to affect the evaluation of the effects of the study intervention on
the currently targeted malignancy.
b. Participants with curatively treated basal cell carcinoma of the skin,
superficial bladder cancer, squamous cell carcinoma of the skin, in situ
cervical cancer, and/or in situ breast cancer may be enrolled in the study.
6. Has known symptomatic, untreated, or actively progressing brain metastases.
a. Participants with non-leptomeningeal brain metastases who have received
prior therapy for brain metastases and have radiographically stable CNS disease
(typically determined with 2 brain scans collected at least 4 weeks apart) may
participate, provided they are neurologically stable (i.e., any neurologic
symptoms that developed either as a result of the brain metastases or their
treatment must have returned to baseline or resolved) for at least 2 weeks
before randomization and have been off corticosteroids for at least 3 days
prior to the date of randomization.
b. Any leptomeningeal
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To evaluate the antitumor activity of novel immunotherapy combinations compared<br /><br>with pembrolizumab in participants with PD-L1-high NSCLC.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* To assess the dose-response relationship of novel immunotherapy combinations<br /><br>across a range of the novel components' dose levels and fixed dostarlimab dose.<br /><br>* To further assess the clinical activity of novel immunotherapy combinations<br /><br>compared with pembrolizumab in participants with PD-L1-high NSCLC.<br /><br>* To evaluate the antitumor activity of novel immunotherapy combinations via<br /><br>treatment arm comparisons for assessment of contribution of components for the<br /><br>combination regimens.<br /><br>* To further characterize the safety of novel immunotherapy combinations.<br /><br>* To determine the immunogenicity of individual agents comprising novel<br /><br>immunotherapy combinations.<br /><br>* To characterize the PK properties of novel immunotherapy combinations</p><br>