Clinical trial NCT06996782: A Platform Study in Non-Small Cell Lung Cancer (NSCLC)
Official title: A Phase Ib/II Open-Label, Multicentre Platform Study Evaluating Novel Combinations in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic Non-small Cell Lung Cancer
Keywords: Checkpoint inhibitor
Platinum-based chemotherapy
Interleukin-2 (IL-2)
T-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) domains (TIGIT)
Programmed death-ligand 1 (PD-L1)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2025-05-30
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of multiple study interventions including novel-novel combinations or novel agents in combination with standard therapy for the treatment of metastatic NSCLC.

Detailed description: This is a multicentre, open-label study to evaluate the safety and efficacy of various combinations of study interventions in participants with advanced or metastatic NSCLC (mNSCLC).

The study will include sub-studies (sub-study 1 and sub-study 2) and each sub-study focused on a specific treatment may include 2 parts -

1. Part A consisting of one of more safety run-in cohorts to evaluate 2 or more dose levels to identify the recommended Phase 2 dose (RP2D) unless RP2D has been established then Part A will not be required; and
2. Part B consisting of one or more expansion cohorts.

Sub-study 1 will investigate the safety, tolerability, and anti-tumour activity of combination of rilvegostomig and AB248.

Sub-study 2 will evaluate the safety, tolerability, and anti-tumour activity of rilvegostomig and standard of care (SoC) platinum-based chemotherapy. Safety run-in (Part A) will not be conducted in sub-study 2.

Eligibility criteria: Inclusion Criteria (both sub study 1 and sub study 2):

* Participants with confirmed squamous or non-squamous NSCLC with a current Stage IV mNSCLC.
* Provision of acceptable archival tumour tissue (or fresh tumour tissue biopsy if archival tumour tissue is not available and if clinically feasible) is mandatory at screening.
* Measurable disease as defined by at least one lesion that can be accurately measured at baseline as ≥ 10 mm at the longest diameter.
* Minimum life expectancy of 12 weeks in the opinion of the investigator.
* Adequate organ and marrow function.
* Contraceptive use by male or female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Adequate organ and marrow function and minimum body weight of 30 Kg.
* PD-L1 tumour proportion score (TPS) ≥ 1% (per local report).

Exclusion Criteria (both sub study 1 and sub study 2):

* Participants with epidermal growth factor receptor mutations, anaplastic lymphoma receptor fusions or any other known genomic alteration for which targeted therapy is approved in the first line per local standard of care.
* Any severe or uncontrolled systemic diseases, including uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; serious chronic gastrointestinal conditions associated with diarrhoea, active non-infectious skin disease or substance abuse.
* Has had a prior stem cell, bone marrow, allogenic tissue, or solid organ transplant.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years.
* History of clinically significant arrhythmia, cardiomyopathy of any aetiology or symptomatic congestive heart failure.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention or presence of small cell and neuroendocrine histology components.
* Unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy, spinal cord compression or symptomatic brain metastases.
* Any prior systemic therapy received for advanced or mNSCLC or treatment with any other anti-cancer agents or immunosuppressive medication.
* Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.
* Active tuberculosis infection.
* Any prior exposure to an anti-T-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) domains (TIGIT) therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
* Any prior systemic treatment with an immune-oncology agent, including but not limited to anti-PD-1, anti-PD-L1, anti-Cytotoxic T-lymphocyte Associated Antigen 4 (CTLA-4).

Exclusion Criteria for Sub study 1:

* Has a known history of human immunodeficiency virus (HIV) infection.
* Has either a known history of Hepatitis B virus or has active Hepatitis C virus.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis/interstitial lung disease.

Exclusion Criteria for Sub study 2:

* Known active hepatitis A, chronic or active hepatitis B, or chronic or active hepatitis C infection.
* Known HIV infection that is not well controlled.

Primary outcomes:
measure: Part A and Part B: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Approximately 46 months
measure: Part A: Number of partcipants with dose limiting toxicity (DLT)
timeFrame: Approximately 46 months
measure: Part B: Objective response (OR)
timeFrame: Approximately 46 months
Secondary outcomes:
measure: Part A: Objective response (OR)
timeFrame: Approximately 46 months
measure: Part A and Part B: Duration of response (DOR)
timeFrame: Approximately 46 months
measure: Part A and Part B: Time to response (TTR)
timeFrame: Approximately 46 months
measure: Part A and Part B: Disease control (DC)
timeFrame: Approximately 46 months
measure: Part A and Part B: Progression free survival (PFS)
timeFrame: Approximately 46 months
measure: Part A and Part B: Progression free survival at 6 months (PFS6)
timeFrame: From Day 1 pre-dose to 6 months
measure: Part A and Part B: Progression free survival at 12 months (PFS12)
timeFrame: From Day 1 pre-dose to 12 months
measure: Part A and Part B: Overall survival (OS)
timeFrame: Approximately 46 months
measure: Part A and Part B: Overall survival at 12 months (OS12)
timeFrame: From Day 1 pre-dose to 12 months
measure: Part A and Part B: Overall survival at 24 months (OS24)
timeFrame: From Day 1 pre-dose to 24 months
measure: Part A and Part B: Serum concentration
timeFrame: Approximately 46 months
measure: Part A and Part B: Maximum plasma drug concentration (Cmax)
timeFrame: Approximately 46 months
measure: Part A and Part B: Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast)
timeFrame: Approximately 46 months
measure: Part A and Part B: Area under plasma concentration-time curve from time 0 to infinity (AUC∞)
timeFrame: Approximately 46 months
measure: Part A and Part B: Time to reach maximum concentration following drug administration (tmax)
timeFrame: Approximately 46 months
measure: Part A and Part B: Terminal elimination half-life (t1/2λz)
timeFrame: Approximately 46 months
measure: Part A and Part B: Clearance (CL)
timeFrame: Approximately 46 months
measure: Part A and Part B: Volume of distribution at terminal phase (Vz)
timeFrame: Approximately 46 months
measure: Part A and Part B: Number of participants with anti-drug antibodies (ADAs)
timeFrame: Approximately 46 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
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state: Minnesota
city: Cleveland
country: United States
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state: Ohio
city: Providence
country: United States
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state: Rhode Island
city: Tyler
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state: Texas
city: Anderlecht
country: Belgium
facility: Research Site
city: Hasselt
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
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city: Natal
country: Brazil
facility: Research Site
city: Pelotas
country: Brazil
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city: Porto Alegre
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city: Sao Paulo
country: Brazil
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city: Sao Paulo
country: Brazil
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city: São Paulo
country: Brazil
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Deyang
country: China
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city: Guangzhou
country: China
facility: Research Site
city: Jinan
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Limoges
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Nice
country: France
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city: Paris
country: France
facility: Research Site
city: Batumi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Seongbuk-Gu
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: 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: Selangor
country: Malaysia
facility: Research Site
city: Singapore
country: Malaysia
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city: Chisinau
country: Moldova, Republic of
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city: Amsterdam
country: Netherlands
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city: Groningen
country: Netherlands
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city: Leiden
country: Netherlands
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city: Lima
country: Peru
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city: Koszalin
country: Poland
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city: Olsztyn
country: Poland
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city: Łódź
country: Poland
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city: Belgrade
country: Serbia
facility: Research Site
city: Belgrad
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
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city: Nis
country: Serbia
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city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Mueang Chanthaburi
country: Thailand
facility: Research Site
city: Rachathewi
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
Study officials:
References: