Study to Assess the Safety and Efficacy of AZD2936 in Participants With Advanced or Metastatic Non-small Cell Lung Cancer (ARTEMIDE-01)

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ClinicalTrials.gov Identifier: NCT04995523

Recruitment Status : Recruiting

First Posted : August 9, 2021

Last Update Posted : May 30, 2023

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

July 16, 2021

First Posted Date ^ICMJE

August 9, 2021

Last Update Posted Date

May 30, 2023

Actual Study Start Date ^ICMJE

September 14, 2021

Estimated Primary Completion Date

December 7, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 [ Time Frame: Part A, B, C and D: From the time of informed consent until 90 days after the last dose of AZD2936 ]
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.
Rate of AZD2936 discontinuation due to toxicity [ Time Frame: Part A, B, C and D: From first dose to the last dose of AZD2936 (an average of 6 months) ]
Percentage of participants with AEs leading to discontinuation of AZD2936
Objective Response Rate (ORR) [ Time Frame: Part B, C and D: From first dose of AZD2936 to progressive disease (PD) or death in the absence of disease progression (approximately 2 years) ]
Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1

Original Primary Outcome Measures ^ICMJE

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 [ Time Frame: Part A, B, C: From the time of informed consent until 90 days after the last dose of AZD2936 ]
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.
Rate of AZD2936 discontinuation due to toxicity [ Time Frame: Part A, B, C: From first dose to the last dose of AZD2936 (an average of 6 months) ]
Percentage of participants with AEs leading to discontinuation of AZD2936
Objective Response Rate (ORR) [ Time Frame: Part B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years) ]
Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1

Change History

Current Secondary Outcome Measures ^ICMJE

ORR [ Time Frame: Part A: From first dose of AZD2936 to PD or death in the absence of disease progression (approximately 2 years). ]
Percentage of participants with a confirmed CR or PR according to RECIST v1.1
Disease control rate (DCR) [ Time Frame: Part A, B, C: From first dose of AZD2936 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). ]
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
Duration of response (DoR) [ Time Frame: Part A, B, C and D: From first dose of AZD2936 to PD or death in the absence of disease progression (approximately 2 years). ]
The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression
Durable response rate (DRR) [ Time Frame: Part A, B, C and D: From first dose of AZD2936 to PD or death in the absence of disease progression (approximately 2 years). ]
The percentage of participants according to RECIST v1.1 with a confirmed CR or PR lasting 6 months or more
Progression-free survival (PFS) [ Time Frame: Part B, C: From first dose of AZD2936 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). ]
The time from first dose of study intervention until the date of objective disease progression or death in the absence of disease progression
Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood [ Time Frame: Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B. ]
Evaluation of the target engagement of AZD2936 in peripheral blood
PK of AZD2936: Maximum plasma concentration of the study drug (Cmax) [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B, C and D. ]
Maximum observed plasma concentration of AZD2936
PK of AZD2936: Area under the concentration-time curve (AUC) [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B, C and D. ]
Area under the plasma concentration-time curve
PK of AZD2936: Clearance [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B, C and D. ]
A pharmacokinetic measurement of the volume of plasma from which the study intervention is completely removed per unit time.
PK of AZD2936: Terminal elimination half-life (t 1/2) [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B, C and D. ]
Terminal elimination half life
Incidence of anti-drug antibodies (ADA) against AZD2936 in serum [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B, C and D. ]
Immunogenicity of AZD2936

Original Secondary Outcome Measures ^ICMJE

ORR [ Time Frame: Part A: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years) ]
Percentage of participants with a confirmed CR or PR according to RECIST v1.1
Disease control rate (DCR) [ Time Frame: Part A, B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years) ]
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
Duration of response (DoR) [ Time Frame: Part A, B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years) ]
The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression
Durable response rate (DRR) [ Time Frame: Part A, B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression (approximately 2 years) ]
The percentage of participants according to RECIST v1.1 with a confirmed CR or PR lasting 6 months or more
Progression-free survival (PFS) [ Time Frame: Part B, C: From first dose of AZD2936 to progressive disease or death in the absence of disease progression. (approximately 2 years) ]
The time from first dose of study intervention until the date of objective disease progression or death in the absence of disease progression
Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood [ Time Frame: Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C. ]
Evaluation of the target engagement of AZD2936 in peripheral blood
PK of AZD2936: Maximum plasma concentration of the study drug (Cmax) [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C. ]
Maximum observed plasma concentration of AZD2936
PK of AZD2936: Area under the concentration-time curve (AUC) [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C. ]
Area under the plasma concentration-time curve
PK of AZD2936: Clearance [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C. ]
A pharmacokinetic measurement of the volume of plasma from which the study intervention is completely removed per unit time.
PK of AZD2936: Terminal elimination half-life (t 1/2) [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C. ]
Terminal elimination half life
Incidence of anti-drug antibodies (ADA) against AZD2936 in serum [ Time Frame: From first dose of study intervention, at predefined intervals throughout the administration of AZD2936 (approximately 2 years). The predefined intervals for Part A will be different from Part B and C. ]
Immunogenicity of AZD2936

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Study to Assess the Safety and Efficacy of AZD2936 in Participants With Advanced or Metastatic Non-small Cell Lung Cancer

Official Title ^ICMJE

Phase I/II, Open-label, Dose Escalation and Dose Expansion Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD2936 Anti-TIGIT/Anti-PD-1 Antibody in Participants With Advanced or Metastatic Non-small Cell Lung Cancer

Brief Summary

This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody, AZD2936 is safe, tolerable and efficacious in participants with Advanced or Metastatic Non-small Cell Lung Cancer.

Detailed Description

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 AZD2936 in adult participants with stage III unresectable or stage IV NSCLC. The study includes 4 parts: Part A (dose escalation) and Parts B-D (dose expansion).

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

The study includes 4 parts: Part A: Dose escalation; B & C: Dose expansion non-randomized; D: Randomized RP2D & alternative dose.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Non-Small-Cell Lung Carcinoma

Intervention ^ICMJE

Drug: AZD2936

Anti-TIGIT/Anti-PD-1 Bispecific Antibody

Other Name: Rilvegostomig

Study Arms ^ICMJE

Experimental: Dose Escalation Part A: Checkpoint inhibitor (CPI) experienced NSCLC
AZD2936 Intravenous (IV) monotherapy

Intervention: Drug: AZD2936
Experimental: Dose Expansion Part B: CPI experienced NSCLC
AZD2936 IV monotherapy

Intervention: Drug: AZD2936
Experimental: Dose Expansion Part C: CPI Naive NSCLC
AZD2936 IV monotherapy

Intervention: Drug: AZD2936
Experimental: Dose Expansion Part D: CPI Naive NSCLC
AZD2936 IV monotherapy

Intervention: Drug: AZD2936

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

192

Original Estimated Enrollment ^ICMJE

147

Estimated Study Completion Date ^ICMJE

July 14, 2025

Estimated Primary Completion Date

December 7, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.
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 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 (Treatment with one previous systemic chemotherapy will be allowed).
Primary or secondary resistance after treatment with 2 or more regimens including a CPI.
Symptomatic central nervous system (CNS) metastasis.
Thromboembolic event within 3 months prior to enrolment.
Other invasive malignancy within 2 years prior to screening.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 130 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Listed Location Countries ^ICMJE

Australia, Belgium, Brazil, China, Denmark, France, Japan, Korea, Republic of, Malaysia, Netherlands, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04995523

Other Study ID Numbers ^ICMJE

D7020C00001
2021-000857-23 ( EudraCT Number )

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	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.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Time Frame:	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.
Access Criteria:	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.
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home