A global phase III study to investigate the effectiveness and safety of Rilvegostomig plus chemotherapy to that of pembrolizumab plus chemotherapy in metastatic non-squamous NSCLC expressing PD-L1.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Feb 2025 → ongoing

Decision date (initial)

2025-01-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-515008-38-00

ClinicalTrials.gov

NCT06627647

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Efficacy, Safety

To demonstrate the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS and PFS

Secondary objectives 6

1. To characterize the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS, PFS, and DoR
2. To compare the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS2.
3. To characterize and compare the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of ORR.
4. To assess the PK of rilvegostomig, patient-reported physical functioning, patient-reported GHS/QoL, and patient-reported lung cancer symptoms of NSCLC.
5. To investigate the immunogenicity of rilvegostomig.
6. To assess the safety and tolerability of rilvegostomig plus chemotherapy compared to pembrolizumab plus chemotherapy.

Conditions and MedDRA coding

Metastatic Non-squamous Non-small Cell Lung Cancer Whose Tumors Express PD-L1

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Please copy information from the IPD instruction placed on sharepoint under link: https://azcollaboration.sharepoint.com/sites/AZ005/Shared%20Documents/Registration_Results_PharmaCM/Registration/IPD_sharing_entry_guidance.pdf

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically or cytologically documented non-squamous NSCLC.
2. Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
3. Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements.
4. Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted 1L therapies.
5. Provision of acceptable tumor sample to confirm tumor PD-L1 expression TC ≥ 1%.
6. At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is suitable for accurate repeated measurements.
7. Adequate organ and bone marrow function.

Exclusion criteria 9

1. Presence of small cell and neuroendocrine histology components.
2. Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 7 Days prior to randomization. A minimum of 2 weeks must have elapsed between the end of local therapy (brain radiotherapy or surgery) and randomization. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure) or surgery prior to randomization.
3. Any prior systemic therapy received for advanced or mNSCLC.
4. Prior treatment with an anti-PD-1 or anti-PD-L1 agent.
5. Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
6. 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 and of low potential risk for recurrence.
7. Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
8. Active primary immunodeficiency/active infectious disease(s).
9. Active tuberculosis infection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall Survival (OS).
2. Progression-free survival (PFS).

Secondary endpoints 10

1. Landmark overall survival (OS) rates
2. Landmark progression-free survival (PFS) rates
3. Time to second progression or death (PFS2)
4. Overall response rate (ORR)
5. Duration of response (DoR)
6. Concentration of rilvegostomig in serum.
7. Presence of antidrug antibody (ADAs), titer and neutralizing antibodies for rilvegostomig.
8. Proportion of participants with maintained or improved physical functioning.
9. Time to deterioration (TTD) of global health status (GHS)/quality of life (QoL) and in pulmonary symptoms.
10. Adverse events (AEs) (graded by CTCAE version 5.0), clinical laboratory assessments, vital signs, and Eastern Cooperative Oncology Group (ECOG) performance status.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Locations

8 EU/EEA countries · 66 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 79 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications