A Platform Study in Non-Small Cell Lung Cancer (NSCLC) (ALTAIR)

AstraZeneca

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Advanced or Metastatic Non-small Cell Lung Cancer

Treatments

Drug: Rilvegostomig

Drug: Paclitaxel

Drug: Pemetrexed

Drug: Cisplatin

Drug: Nab-paclitaxel

Drug: Ramucirumab

Drug: AB248

Drug: Carboplatin

Study type

Interventional

Funder types

Industry

Identifiers

NCT06996782

D702KC00001

2024-519786-22 (Other Identifier)

Details and patient eligibility

About

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.

Full 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 -

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
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 plus standard of care (SoC) platinum-based chemotherapy, with or without ramucirumab.

Enrollment

182 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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).

Inclusion Criteria for Sub Study 2:

Adequate coagulation and urinalysis.

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 (HBV) or has active Hepatitis C virus (HCV).
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis/interstitial lung disease.
Any concomitant medication known to be associated with Torsades de pointes.

Exclusion Criteria for Sub Study 2:

Known active hepatitis A.
Acute hepatitis B infection (anti-hepatitis B core antibody [HBc] immunoglobulin M [IgM] positive) or chronic hepatitis B infection with HBV DNA ≥ 2000 IU/mL.
Active hepatitis C infection (anti-HCV positive with HCV RNA detectable) or anti- HCV positive with HCV RNA undetectable for less than 12 weeks following treatment for HCV.
Known HIV infection that is not well controlled.
Evidence of Grade ≥ 1 central nervous system (CNS) haemorrhage.
Uncontrolled arterial hypertension ≥ 150 and/or ≥ 100 mm Hg.
Radiographic evidence of major blood vessel invasion or encasement by cancer, intratumour cavitation or direct tumour penetration into the trachea or bronchus.
Has experienced any arterial thrombotic event, a Grade ≥ 3 bleeding event or has gross haemoptysis.
Has significant bleeding disorders, serious or nonhealing wound, ulcer or clinically relevant congestive heart failure.
Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
Under chronic therapy with antiplatelet agents.
Any prior exposure to anti-vascular endothelial growth factor (VEGF) therapy.
Known allergy or hypersensitivity to rilvegostomig or any of the excipients of rilvegostomig, cisplatin, carboplatin, paclitaxel or nab-paclitaxel or pemetrexed or ramucirumab.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

182 participants in 4 patient groups

Sub study 1 Part A: Safety run-in

Experimental group

Description:

Participants will receive AB248 in combination with rilvegostomig to identify the RP2D to futher evaluate the combination in Part B.

Treatment:

Drug: AB248

Drug: Rilvegostomig

Sub study 1 Part B: Dose expansion

Experimental group

Description:

Participants with squamous and non-squamous NSCLC (programmed death-ligand 1 \[PD-L1\] ≥ 50% and PD-L1 1-49%) will receive AB248 in combination with rilvegostomig based on the RP2D determined in Part A.

Treatment:

Drug: AB248

Drug: Rilvegostomig

Sub study 2 Part A: Safety run-in

Experimental group

Description:

Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen.

Treatment:

Drug: Carboplatin

Drug: Ramucirumab

Drug: Nab-paclitaxel

Drug: Pemetrexed

Drug: Cisplatin

Drug: Paclitaxel

Drug: Rilvegostomig

Sub study 2 Part B: Dose expansion

Experimental group

Description:

Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts.

Treatment:

Drug: Carboplatin

Drug: Ramucirumab

Drug: Nab-paclitaxel

Drug: Pemetrexed

Drug: Cisplatin

Drug: Paclitaxel

Drug: Rilvegostomig