Clinical trial • Phase III • Oncology

RILVEGOSTOMIG for Non-small cell lung cancer (non-squamous, metastatic; PD-L1 expressing)

Phase III trial of RILVEGOSTOMIG for Non-small cell lung cancer (non-squamous, metastatic; PD-L1 expressing).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer (non-squamous, metastatic; PD-L1 expressing)
Trial Stage
Phase III
Drug Modality
Bispecific antibody|Monoclonal antibody|Small molecule

Key dates

Initial CTIS Submission Date
13-09-2024
First CTIS Authorization Date
21-01-2025

Trial design

Randomised, arm b: pembrolizumab (keytruda 25 mg/ml concentrate for solution for infusion) administered intravenously in combination with platinum-based chemotherapy (cisplatin or carboplatin plus pemetrexed), followed by pembrolizumab monotherapy plus pemetrexed in maintenance (specific dose/schedule not stated in supplied data).-controlled Phase III trial in Italy, Netherlands, France and others.

Randomised
Yes
Comparator
Arm B: Pembrolizumab (KEYTRUDA 25 mg/mL concentrate for solution for infusion) administered intravenously in combination with platinum-based chemotherapy (cisplatin or carboplatin plus pemetrexed), followed by pembrolizumab monotherapy plus pemetrexed in maintenance (specific dose/schedule not stated in supplied data).
Target Sample Size
637

Eligibility

Recruits 637 Vulnerable population selected (isVulnerablePopulationSelected = true). Provided materials include subject information sheets and informed consent forms for adult participants (multiple language versions listed). No explicit details on assent or additional consent procedures for minors or other vulnerable groups are provided in the supplied data..

Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected = true). Provided materials include subject information sheets and informed consent forms for adult participants (multiple language versions listed). No explicit details on assent or additional consent procedures for minors or other vulnerable groups are provided in the supplied data.

Inclusion criteria

  • {"criterion_text":"- Histologically or cytologically documented non-squamous NSCLC.\n- Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.\n- 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.\n- 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.\n- Provision of acceptable tumor sample to confirm tumor PD-L1 expression TC ≥ 1%.\n- 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.\n- Adequate organ and bone marrow function."}

Exclusion criteria

  • {"criterion_text":"- Presence of small cell and neuroendocrine histology components.\n- 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.\n- Any prior systemic therapy received for advanced or mNSCLC.\n- Prior treatment with an anti-PD-1 or anti-PD-L1 agent.\n- Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.\n- 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.\n- Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.\n- Active primary immunodeficiency/active infectious disease(s).\n- Active tuberculosis infection."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Overall Survival (OS).","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Progression-free survival (PFS).","definition_or_measurement_approach":""}

Secondary endpoints

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

Recruitment

Planned Sample Size
637
Recruitment Window Months
64
Consent Approach
Informed consent obtained using subject information sheets and informed consent forms (SIS and ICF). Multiple language versions of SIS/ICF are listed (English, French, Polish, Dutch, Spanish, Italian, German, Hungarian, etc.). Specific consenting party: adult participants provide informed consent. Additional ICFs exist for optional genomic research and for pregnant partners; no further procedural details (assent processes or age-specific consent workflow) are provided in the supplied data.

Geography

Total Number Of Participants
241

Italy

Earliest CTIS Part Ii Submission Date
30-09-2024
Latest Decision Or Authorization Date
05-12-2025
Processing Time Days
431
Number Of Participants
17

Netherlands

Earliest CTIS Part Ii Submission Date
18-12-2024
Latest Decision Or Authorization Date
02-12-2025
Processing Time Days
349
Number Of Participants
15

France

Earliest CTIS Part Ii Submission Date
28-10-2024
Latest Decision Or Authorization Date
04-12-2025
Processing Time Days
402
Number Of Participants
33

Poland

Earliest CTIS Part Ii Submission Date
10-01-2025
Latest Decision Or Authorization Date
03-12-2025
Processing Time Days
327
Number Of Participants
21

Spain

Earliest CTIS Part Ii Submission Date
09-12-2024
Latest Decision Or Authorization Date
02-12-2025
Processing Time Days
358
Number Of Participants
40

Hungary

Earliest CTIS Part Ii Submission Date
15-11-2024
Latest Decision Or Authorization Date
20-01-2026
Processing Time Days
431
Number Of Participants
36

Belgium

Earliest CTIS Part Ii Submission Date
06-12-2024
Latest Decision Or Authorization Date
01-12-2025
Processing Time Days
360
Number Of Participants
21

Germany

Earliest CTIS Part Ii Submission Date
10-12-2024
Latest Decision Or Authorization Date
03-12-2025
Processing Time Days
358
Number Of Participants
58

Sponsor

Primary sponsor

Full Name
AstraZeneca AB
Organisation Type
Pharmaceutical company
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
Rilvegostomig
Active Substance
RILVEGOSTOMIG
Modality
Bispecific antibody
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS
Authorisation Status
Investigational (prodAuthStatus 1)
Investigational Product Name
KEYTRUDA 25 mg/mL concentrate for solution for infusion
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS
Authorisation Status
Authorised (EU/1/15/1024/002)
Maximum Dose
200 mg (maxDailyDoseAmount indicated in product entry)
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS
Authorisation Status
Known medicinal product (prodAuthStatus 2)
Investigational Product Name
CISPLATIN
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENIOUS INFUSION
Authorisation Status
Known medicinal product (prodAuthStatus 2)
Investigational Product Name
PEMETREXED
Active Substance
PEMETREXED
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Known medicinal product (prodAuthStatus 2)
Investigational Product Name
INFLIXIMAB
Active Substance
INFLIXIMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENIOUS INFUSION
Authorisation Status
Known medicinal product (prodAuthStatus 2)
Investigational Product Name
MYCOPHENOLATE MOFETIL
Active Substance
MYCOPHENOLATE MOFETIL
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Known medicinal product (prodAuthStatus 2)
Combination Treatment
Yes

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