Undersøgelse for at vurdere sikkerheden og effektiviteten af AZD2936 hos deltagere med avanceret eller metastatisk ikke-småcellet lungekræft (ARTEMIDE-01)
Fase I/II, åben-label, dosiseskalering og dosisudvidelsesundersøgelse til evaluering af sikkerhed, farmakokinetik, farmakodynamik og effektivitet af AZD2936 Anti-TIGIT/Anti-PD-1 antistof hos deltagere med avanceret eller metastatisk ikke-småcellet lungekræft
This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and efficacious in participants with Advanced or Metastatic Non-small Cell Lung Cancer.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
This is a first-time-in-human (FTIH), open-label, multicenter, multi-part, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of rilvegostomig (AZD2936) in adult participants with stage III unresectable or stage IV NSCLC. The study includes 4 parts: Part A (dose escalation) and Parts B-E (dose expansion).
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
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Melbourne, Australien, 3000
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Anderlecht, Belgien, 1070
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Leuven, Belgien, 3000
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Florianópolis, Brasilien, 88034-000
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Natal, Brasilien, 59075-740
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Porto Alegre, Brasilien, 90035903
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Rio de Janeiro, Brasilien, 20231-050
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São Paulo, Brasilien, 01246-000
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Copenhagen, Danmark, 2100
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Illinois
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Chicago, Illinois, Forenede Stater, 60637
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
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Virginia
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Fairfax, Virginia, Forenede Stater, 22031
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Dijon, Frankrig, 21079
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Toulouse, Frankrig, 31059
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Tbilisi, Georgien, 0112
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Groningen, Holland, 9713 GZ
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Leiden, Holland, 2333 ZA
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Utrecht, Holland, 3584 CX
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Kashiwa, Japan, 227-8577
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Niigata, Japan, 951-8566
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Sendai, Japan, 981-0914
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Tokyo, Japan, 104-0045
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Chengdu, Kina, 610041
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Chongqing, Kina, 400030
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Kuala Lumpur, Malaysia, 59100
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Kuching, Malaysia, 93586
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Chisinau, Moldova, MD-2025
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Barcelona, Spanien, 08035
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Madrid, Spanien, 28041
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Madrid, Spanien, 28027
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Seoul, Sydkorea, 03722
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Seoul, Sydkorea, 05505
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Seoul, Sydkorea, 03082
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Taichung, Taiwan, 40705
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Taichung, Taiwan, 40201
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Tainan, Taiwan, 70403
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Taipei, Taiwan, 110
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Bangkok, Thailand, 10700
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Chanthaburi, Thailand, 22000
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Muang, Thailand, 50200
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Written informed consent
- Aged 18 or above
- Part A and Part B: Unresectable stage III or stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. Part C and Part D: Stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. Part E: Stage IV squamous NSCLC not amenable to curative surgery or radiation.
- Documented PD-L1 expression by PD-L1 IHC per local report.
- Part A and Part B: Confirmed progression during treatment with a CPI-including regimen.
- Part C and Part D: No prior I/O treatment for metastatic NSCLC.
- Part E: No prior treatment for metastatic NSCLC.
- ECOG performance status of 0 or 1 at enrolment.
- Life expectancy of ≥ 12 weeks at enrolment.
- Have at least 1 measurable lesion per RECIST v1.1.
- Adequate bone marrow, liver and kidney function
Exclusion Criteria:
- Sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusion
- Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (e.g. ROS1, NTRK fusions, BRAF, V600E mutation)
- Previous treatment with an anti-TIGIT therapy
- Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
- Part A and Part B: Primary or secondary resistance after treatment with 2 or more regiments including a CPI.
- Part C and Part D: Any prior systemic treatment with an immune oncology agent (prior administration of immune-oncology agent for curative intent to treat other invasive malignancy is permitted).
Treatment with one previous systemic chemotherapy will be allowed.
- Part E: Any prior systemic treatment for metastatic NSCLC, including but not limited to chemotherapy, anti-PD-1, anti-PD-L1, anti-CTLA-4.
- Symptomatic central nervous system (CNS) metastasis.
- Thromboembolic event within 3 months prior to enrolment.
- Other invasive malignancy within 2 years prior to screening.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Dose Escalation Part A: Checkpoint inhibitor (CPI) experienced Non-small Cell Lung Cancer (NSCLC)
Rilvegostomig Intravenous (IV) monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Andre navne:
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Eksperimentel: Dose Expansion Part B: CPI experienced NSCLC
Rilvegostomig IV monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Andre navne:
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Eksperimentel: Dose Expansion Part C: CPI Naive NSCLC
Rilvegostomig IV monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Andre navne:
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Eksperimentel: Dose Expansion Part D: CPI Naive NSCLC
Rilvegostomig IV monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Andre navne:
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Eksperimentel: Dose Expansion Part E: treatment Naive Squamous NSCLC
Rilvegostomig IV monotherapy |
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Percentage of participants with adverse events (AEs) and immune mediated AEs (imAEs), serious AEs (SAEs), dose limiting toxicities (DLTs), vital signs, and abnormal laboratory parameters
Tidsramme: Part A, B, C, D and E: From the time of informed consent until 90 days after the last dose of rilvegostomig
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A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness. |
Part A, B, C, D and E: From the time of informed consent until 90 days after the last dose of rilvegostomig
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Rate of rilvegostomig discontinuation due to toxicity
Tidsramme: Part A, B, C, D and E: From first dose to the last dose of rilvegostomig (an average of 6 months)
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Percentage of participants with AEs leading to discontinuation of rilvegostomig |
Part A, B, C, D and E: From first dose to the last dose of rilvegostomig (an average of 6 months)
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Objective Response Rate (ORR)
Tidsramme: Part B, C, D and E: From first dose of rilvegostomig to progressive disease (PD) or death in the absence of disease progression (approximately 2 years)
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Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 |
Part B, C, D and E: From first dose of rilvegostomig to progressive disease (PD) or death in the absence of disease progression (approximately 2 years)
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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ORR
Tidsramme: Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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Percentage of participants with a confirmed CR or PR according to RECIST v1.1 |
Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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Disease control rate (DCR)
Tidsramme: Part A, B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).
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Percentage of participants who have a best objective response of confirmed CR or PR or who have SD lasting for at least a certain time of period after start of treatment |
Part A, B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).
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Duration of response (DoR)
Tidsramme: Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression |
Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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Durable response rate (DRR)
Tidsramme: Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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The percentage of participants according to RECIST v1.1 with a confirmed CR or PR lasting 6 months or more |
Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
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Progression-free survival (PFS)
Tidsramme: Part B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).
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The time from first dose of study intervention until the date of objective disease progression or death in the absence of disease progression |
Part B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years).
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Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood
Tidsramme: Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B.
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Evaluation of the target engagement of rilvegostomig in peripheral blood |
Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B.
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PK of rilvegostomig: Maximum plasma concentration of the study drug (Cmax)
Tidsramme: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Maximum observed plasma concentration of rilvegostomig |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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PK of rilvegostomig: Area under the concentration-time curve (AUC)
Tidsramme: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Area under the plasma concentration-time curve |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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PK of rilvegostomig: Clearance
Tidsramme: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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A pharmacokinetic measurement of the volume of plasma from which the study intervention is completely removed per unit time. |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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PK of rilvegostomig: Terminal elimination half-life (t 1/2)
Tidsramme: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Terminal elimination half life |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Incidence of anti-drug antibodies (ADA) against rilvegostomig in serum
Tidsramme: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Immunogenicity of rilvegostomig |
From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E.
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Samarbejdspartnere og efterforskere
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Neoplasmer efter sted
- Neoplasmer
- Luftvejssygdomme
- Lungesygdomme
- Neoplasmer i luftvejene
- Thoracale neoplasmer
- Neoplastiske processer
- Lungeneoplasmer
- Karcinom, bronkogent
- Bronkiale neoplasmer
- Patologiske tilstande, tegn og symptomer
- Neoplasma Metastase
- Karcinom, ikke-småcellet lunge
- Parkinson Disease 4, Autosomal Dominant Lewy Body
Andre undersøgelses-id-numre
- D7020C00001
- 2021-000857-23 (EudraCT nummer)
- 2023-508262-15-00 (Registry Identifier: EU CT Number)
- 2023 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.
All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD-delingstidsramme
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD-delingsadgangskriterier
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level datain an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
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