A Study of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC (ARTEMIDE-01)

A Study of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC

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 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC

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.

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-D (dose expansion).

TIGIT, Anti-TIGIT, PD-1, Anti-PD-1, NSCLC, Non-small Cell Lung Cancer, Advanced, Metastatic, Solid Tumor, Solid Tumour, Stage 3 NSCLC, Stage III NSCLC, Stage 4 NSCLC, Stage IV NSCLC, PD L1+ tumors

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

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

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 and D: From the time of informed consent until 90 days after the last dose of rilvegostomig

Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1

Part B, C and D: From first dose of rilvegostomig to progressive disease (PD) or death in the absence of disease progression (approximately 2 years)

Part A: From first dose of rilvegostomig 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

Part A, B, C: 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).

The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression

Part A, B, C and D: From first dose of rilvegostomig 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

Part A, B, C and D: From first dose of rilvegostomig 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

Part B, C: 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).

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.

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 and D.

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 and D.

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 and D.

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 and D.

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 and D.

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.

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.

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.

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.