Clinical trial NCT04995523: A Study of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Small-Cell Lung Carcinoma
Keywords: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-08-09
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study includes 5 parts: Part A: Dose escalation; B \& C \& E: Dose expansion non-randomized; D: Randomized RP2D \& alternative dose.
Primary purpose: TREATMENT

Brief summary: 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.

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 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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Part A, B, C, D and E: From the time of informed consent until 90 days after the last dose of rilvegostomig
measure: Rate of rilvegostomig discontinuation due to toxicity
timeFrame: Part A, B, C, D and E: From first dose to the last dose of rilvegostomig (an average of 6 months)
measure: Objective Response Rate (ORR)
timeFrame: 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)
Secondary outcomes:
measure: ORR
timeFrame: Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
measure: Disease control rate (DCR)
timeFrame: 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).
measure: Duration of response (DoR)
timeFrame: 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).
measure: Durable response rate (DRR)
timeFrame: 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).
measure: Progression-free survival (PFS)
timeFrame: 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).
measure: Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood
timeFrame: 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.
measure: PK of rilvegostomig: Maximum plasma concentration of the study drug (Cmax)
timeFrame: 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.
measure: PK of rilvegostomig: Area under the concentration-time curve (AUC)
timeFrame: 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.
measure: PK of rilvegostomig: Clearance
timeFrame: 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.
measure: PK of rilvegostomig: Terminal elimination half-life (t 1/2)
timeFrame: 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.
measure: Incidence of anti-drug antibodies (ADA) against rilvegostomig in serum
timeFrame: 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.
Other outcomes:
Locations:
city: Orange
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Melbourne
country: Australia
facility: Research Site
city: Anderlecht
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Florianópolis
country: Brazil
facility: Research Site
city: Natal
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Copenhagen
country: Denmark
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Chisinau
country: Moldova, Republic of
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Mueang Chanthaburi
country: Thailand
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
References: