Lungcancer Non-small cell lungcarcinoma
Conditions
Interventions
Following an initial screening period of up to 28 days, eligible participants
will receive AZD2936 (rilvegostomig) every 3 weeks (Q3W) administered via
intravenous (IV) infusion at the selected dose
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Disease for part D only: •Stage IV squamous or non-squamous NSCLC. •PD-L1 TPS >= 50% •provision of archival tumor tissue (or fresh tumor tissue biopsy must be confirmed if archival tumor tissue is not available and if clinically feasible) is mandatory at screening for all study parts •No sensitizing EGFR mutations or ALK fusions. •No documented test result for other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (ROS1, NTRK fusions, BRAF, V600E mutation, etc.) Prior therapy: •Part D (Dose Expansion): Must meet one of the definitions below: (i) No prior treatment for NSCLC, and not in need of rapid disease control via chemotherapy-containing regimen, or (ii) Prior treatment for NSCLC with one regimen consisting of chemotherapy only. •No unresolved toxicities of >= Grade 2 (CTCAE v5.0) from prior therapy (excluding vitiligo, alopecia, endocrine disorders that are controlled with replacement hormone therapy, asymptomatic laboratory abnormalities). Overall condition: •ECOG performance status 0 or 1 at enrolment. •Life expectancy of >= 12 weeks at enrolment. •Adequate bone marrow, liver and kidney function.
Exclusion criteria
Exclusion criteria: - Participants with either of the following are excluded: (a) Sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase fusions (documented test result is mandatory for patients with non-squamous histology). For patients with squamous histology mutation, testing is mandatory only if participant is a never smoker or in the presence of a mixed histology. (b) Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (eg, ROS1, NTRK fusions, BRAF, V600E mutation, etc). - part D only: Any prior systemic treatment with an immune-oncology agent, including but not limited to anti-PD-1, anti-PD-L1, anti-CTLA-4. Treatment with one previous systemic chemotherapy will be allowed. - Symptomatic central nervous system (CNS) metastasis. (a) Note: Participants with known CNS lesions should be asymptomatic, adequately treated with stereotactic radiation therapy, craniotomy, gamma knife therapy, or whole brain radiotherapy, with no subsequent evidence of CNS progression (documented with magnetic resonance imaging [MRI] scans showing the absence of brain metastasis progression after radiotherapeutic intervention); participants must not require steroid exceeding 10 mg prednisone or 2 mg/day of dexamethasone or equivalent; participants with a history of CNS metastases must have MRI of the brain at screening. Participants with CNS metastases who are receiving steroids must be on a stable dose of steroids for >= 7 days prior to study entry and prior to baseline imaging. - Thromboembolic event within 3 months before the first dose of investigational product. - History of organ transplant. - Active primary immunodeficiency/active infectious disease(s): (a) Active infection including tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination, and radiographic findings and TB testing in line with local practice). (b) Human immunodeficiency virus (HIV) (positive for HIV-1 or HIV-2 antibodies). (c) Chronic or active hepatitis B, chronic or active hepatitis C; however, participants who have chronic hepatitis B and are receiving suppressive antiviral therapy are allowed to be enrolled if alanine aminotransferase (ALT) is normal and viral load is controlled. Controlled hepatitis B viral load is defined as serum hepatitis B virus DNA < 100 U/mL by polymerase chain reaction (PCR). Participants with controlled hepatitis B viral load must remain on antiviral therapy, per institutional practice, during the study treatment and follow-up period to ensure adequate viral suppression. Participants who have chronic hepatitis C are allowed to be enrolled if ALT is normal and hepatitis C virus (HCV) RNA undetectable by PCR, either spontaneously or in response to a successful prior course of anti-hepatitis C therapy (Regev et al, 2020).Controlled hepatitis C viral load is defined as undetectable hepatitis C RNA by PCR either spontaneously or in response to a successful prior course of anti-hepatitis C therapy. (d) Acute hepatitis A. (e) For all participants in the study, all local institutional standards for coronavirus disease 2019 (COVID-19) must be followed for testing. For participants with a known previous COVID-19 infection, either
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part D dose expansion: - Percentage of participants at each dose levelwith AEs and imAEs, SAEs, DLT-like events, vital signs, and abnormal laboratory parameters - Rate of AZD2936 (rilvegostomig) discontinuation due to toxicity at each dose level | — |
Secondary
| Measure | Time frame |
|---|---|
| Part D dose expansion: - According to RECIST v1.1: • DCR • DoR • DRR • Progression-free survival (PFS) All parts of the study: - PK parameters to be evaluated include Cmax, AUC, clearance, and t1/2 - Incidence of anti-drug antibodies (ADAs) against AZD2936 (rilvegostomig) in serum Exploratory - Assessment of antitumor activity will be evaluated by measuring and profiling ctDNA changes - Assessment of changes in tumor- and immune-associated marker profiles will be investigated in peripheral blood and tumor tissue biopsies by DNA, RNA, or protein measures, including but not limited to: • Changes in the frequency and profile of T-cell populations such as activated/proliferating T cells by flow cytometry (CD8+ Ki67+), by gene expression (IFN-γ and T effector gene signatures), and by IHC (CD8) as well as T cell repertoire by high-throughput sequencing • Changes in tumor-associated and immune-mediator proteins, including but not limited to serum/plasma levels of chemokines and cytokines (IFN-γ, CXCL9) - Assessment of baseline tumor- and immune-associated marker profiles will be investigated in peripheral blood and tissue biopsies (tumor or non-tumor) by DNA, RNA, or protein measures, including but not limited to: • Baseline expression levels of TIGIT, PD-L1, PD-1, CD8 and IFN-γ gene signature in relation to clinical outcomes evaluated by IHC and/or gene expression • Baseline peripheral immune cell profile and tumor-associated and immune-mediator proteins in relation to clinical outcomes evaluated by flow cytometry, high-throughput sequencing and proteomics • Baseline tumor mutational burden and profile in relation to clinical outcomes evaluated by high-throughput DNA sequencing | — |
Countries
Netherlands
Outcome results
None listed