First-line immunotherapy-based standard of care and local ablative treatments for oligometastatic non-small cell lung cancer patients: a randomized, multicentre, open-label phase III study (OliGRAIL)

Start 6 Mar 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 22 sites · Protocol CSET N° 2023/3729

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ongoing, recruiting

Participants planned 130

Countries 1

Sites 22

Synchronous oligometastatic non-small cell lung cancer (NSCLC)

To demonstrate the survival benefit of adding a radical local treatment (RLT) on a maximum of 5 secondary lesions in non-small cell lung cancer (NSCLC) patients receiving standard of care (SoC)-based immunotherap

Key facts

Sponsor: Institut Gustave Roussy
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Immune System Diseases [C20], Diseases [C] - Respiratory Tract Diseases [C08]
Trial duration: 6 Mar 2025 → ongoing
Decision date (initial): 2024-11-19
Transition trial: No
Low-intervention: Yes
Rare-disease indication: No
Vulnerable population: Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Secondary objectives 7

To compare progression-free survival (PFS), iPFS, cancer-specific survival, patterns of relapse between the two arms.
To compare the frequency and severity of adverse events between the two arms.
To compare patient-reported outcomes (PROs) / quality of life (QoL).
To assess the circulating tumour DNA clearance.
To assess the cost-utility (cost per QALY) of RLT + immunotherapy-based SoC compared to immunotherapy-based SoC alone (economic evaluation).
To explore the effect of RLT modality (minimally invasive surgery vs stereotactic body radiation therapy (SBRT) vs interventional radiology) on OS and local control.
To explore the impact of metastatic site (e.g., brain-only vs. others) on OS and local control.

Conditions and MedDRA coding

Synchronous oligometastatic non-small cell lung cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

Histologically proven advanced oligometastatic stage IV NSCLC.
Patient should understand, sign, and date the informed consent form written in French prior to any protocol-specific procedures performed.
Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 6 months after completing treatment/therapy.
Patients affiliated to the social security system.
Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations including follow-up.
Aga > 18 years
NSCLC patients eligible first line immunotherapy-based SoC according to the European Marketing Authorization. PDL1 status available.
Metastases eligible to RLT(minimally invasive surgery, SBRT and/or interventional radiology) according to the local multidisciplinary board (MTB): ≤5cm each in CT scan, excluding primary tumour.
Maximum 5 metastases in 3 organs (EORTC criteria), according to brain MRI and FDG-PET
Symptomatic lesions requiring urgent palliative radiation, is permitted prior to randomization. These treated lesions should be counted towards the total number of metastases at the time of enrolment.
Clinically required brain metastases (BM) ablation (surgery and/or SBRT) is permitted and BM count within the total number of 5 lesions. The patient would then be randomized to treatment of their remaining disease
Acceptable organ function for RLT
ECOG performance status (PS) 0-1.
Measurable lesions according to RECIST V1.1 or evaluable disease on standard imaging,

Exclusion criteria 5

Non-squamous NSCLC with targetable tumour mutations and approved first line targeted therapy (such as EGFR, ALK and ROS1).
Metastases not eligible to RLT: e.g. brainstem or diffuse serosal metastases (meningeal, pericardial, pleural, peritoneal, mesenteric) or that invades the gastrointestinal tract.
Uncontrolled severe comorbidity, including but not limited to symptomatic interstitial lung disease or active infection.
Prior therapy with T-cell costimulation or immune checkpoint-targeted agents within 1 year.
Uncontrolled concomitant (<1-year) malignancy except adequately treated basal or squamous cell carcinoma of the skin, or in-situ carcinoma of any organ or in-situ melanoma of the skin.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

The primary endpoint is overall survival (OS).

Secondary endpoints 9

PFS or iPFS according to RECIST 1.1 and iRECIST.
Cancer specific survival.
Type of relapses, local and distant control rates in both arms.
Acute/ late adverse events graded by CTCAE v5 (toxic death and serious adverse events).
QoL according to EORTC QLQ-C30, QLQ-LC-13, EQ-5D-5L
Clearance rate at 6 weeks and 4 months (before maintenance) of circulating tumour DNA assessed in plasma compared to value at baseline in the 2 arms.
Economic evaluation: incremental cost per Quality-adjusted life year (QALY based on EQ-5D-5L measures), incremental net monetary benefit.
Effect of RLT modality (minimally invasive surgery vs stereotactic body radiation therapy (SBRT) vs interventional radiology) on OS and local control.
Impact of metastatic site (e.g., brain-only vs. others) on OS and local control.

Investigational products

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

Test 11

Tecentriq 840 mg concentrate for solution for infusion

PRD7537923 · Product

Active substance: Atezolizumab
Substance synonyms: RO5541267
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 1200 mg milligram(s)
Max total dose: 72000 mg milligram(s)
Max treatment duration: 17 Month(s)
Authorisation status: Authorised
ATC code: L01FF05 — -
Marketing authorisation: EU/1/17/1220/002
MA holder: ROCHE REGISTRATION GMBH
MA country: Iceland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

IMJUDO 20 mg/ml concentrate for solution for infusion.

PRD10239823 · Product

Active substance: Tremelimumab
Substance synonyms: CP-675,206, Ticilimumab, MEDI1123
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INFUSION
Max daily dose: 75 mg milligram(s)
Max total dose: 75 mg milligram(s)
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01FX20 — -
Marketing authorisation: EU/1/22/1713/002
MA holder: ASTRAZENECA AB
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

PACLITAXEL SANDOZ 6 mg/ml, solution à diluer pour perfusion

PRD5491070 · Product

Active substance: Paclitaxel
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 200 mg/m2 milligram(s)/square meter
Max total dose: 800 mg/m2 milligram(s)/square meter
Max treatment duration: 4 Month(s)
Authorisation status: Authorised
ATC code: L01CD01 — PACLITAXEL
Marketing authorisation: 34009 568 516 1 4
MA holder: SANDOZ
MA country: France
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

YERVOY 5 mg/ml concentrate for solution for infusion

PRD2341715 · Product

Active substance: Ipilimumab
Substance synonyms: BMS734016, HLX13, IBI310
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 1 mg/kg milligram(s)/kilogram
Max total dose: 60 mg/kg milligram(s)/kilogram
Max treatment duration: 17 Month(s)
Authorisation status: Authorised
ATC code: L01FX04 — -
Marketing authorisation: EU/1/11/698/001
MA holder: BRISTOL-MYERS SQUIBB PHARMA EEIG
MA country: Iceland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

LIBTAYO 350 mg concentrate for solution for infusion.

PRD7514333 · Product

Active substance: Cemiplimab
Substance synonyms: REGN2810
Pharmaceutical form: CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 350 mg milligram(s)
Max total dose: 21000 mg milligram(s)
Max treatment duration: 17 Month(s)
Authorisation status: Authorised
ATC code: L01XC33 — -
Marketing authorisation: EU/1/19/1376/001
MA holder: REGENERON IRELAND D.A.C.
MA country: Iceland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323105 · Product

Active substance: Pembrolizumab
Substance synonyms: Lambrolizumab, MK-3475, SCH-900475, BAT3306, Pabolizumab, FYB206, ABP 234
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 400 mg milligram(s)
Max total dose: 24000 mg milligram(s)
Max treatment duration: 17 Month(s)
Authorisation status: Authorised
ATC code: L01FF02 — -
Marketing authorisation: EU/1/15/1024/002
MA holder: MERCK SHARP & DOHME B.V.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Pemetrexed Accord 25 mg/ml concentrate for solution for infusion

PRD8506964 · Product

Active substance: Pemetrexed
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 500 mg/m2 milligram(s)/square meter
Max total dose: 2000 mg/m2 milligram(s)/square meter
Max treatment duration: 4 Week(s)
Authorisation status: Authorised
ATC code: L01BA04 — -
Marketing authorisation: EU/1/15/1071/004
MA holder: ACCORD HEALTHCARE S.L.U.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

IMFINZI 50 mg/mL concentrate for solution for infusion

PRD6651398 · Product

Active substance: Durvalumab
Substance synonyms: MEDI4736
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INFUSION
Max daily dose: 10 mg/kg milligram(s)/kilogram
Max total dose: 10 mg/kg milligram(s)/kilogram
Max treatment duration: 12 Month(s)
Authorisation status: Authorised
ATC code: L01FF03 — -
Marketing authorisation: EU/1/18/1322/001
MA holder: ASTRAZENECA AB
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cisplatine Accord 1 mg/ml concentraat voor oplossing voor infusie

PRD1951586 · Product

Active substance: Cisplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 6 mg milligram(s)
Max total dose: 2760 mg milligram(s)
Max treatment duration: 4 Month(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: RVG 104068
MA holder: ACCORD HEALTHCARE B.V.
MA country: Netherlands
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

OPDIVO 10 mg/mL concentrate for solution for infusion.

PRD2941372 · Product

Active substance: Nivolumab
Substance synonyms: BMS936558, ABP 206
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 360 mg milligram(s)
Max total dose: 21600 mg milligram(s)
Max treatment duration: 17 Month(s)
Authorisation status: Authorised
ATC code: L01FF01 — -
Marketing authorisation: EU/1/15/1014/001
MA holder: BRISTOL-MYERS SQUIBB PHARMA EEIG
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

CARBOPLATINE KABI 10 mg/ml, solution à diluer pour perfusion

PRD3247178 · Product

Active substance: Carboplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 6 mg milligram(s)
Max total dose: 300 mg milligram(s)
Max treatment duration: 4 Month(s)
Authorisation status: Authorised
ATC code: L01XA02 — CARBOPLATIN
Marketing authorisation: 34009 583 860 1 5
MA holder: FRESENIUS KABI FRANCE S.A.S.
MA country: France
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Gustave Roussy

Sponsor organisation: Institut Gustave Roussy
Address: 114 Rue Edouard Vaillant
City: Villejuif
Postcode: 94800
Country: France

Scientific contact point

Organisation: Institut Gustave Roussy
Contact name: Chargée d'affaires réglementaires

Public contact point

Organisation: Institut Gustave Roussy
Contact name: Chargée d'affaires réglementaires

Locations

1 EU/EEA country · 22 investigational sites

By country

Country	MS status	Planned subjects	Sites
France	Ongoing, recruiting	130	22
Rest of world	—	0	—

Investigational sites

France

22 sites · Ongoing, recruiting

Centre Hospitalier Universitaire Rouen

pneumology (thoracic oncology unit), 1 Rue De Germont, 76000, Rouen

Fondation Hopital Saint Joseph

pneumo oncology and allergology department, 185 Rue Raymond Losserand, 75014, Paris

Institut Sainte Catherine

ONCOLOGIE, 250 Chemin De Baigne Pieds, 84000, Avignon

Institut de Cancérologie du Gard

ONCOLOGIE, Rue du Pr Henri Pujol, 30000, NIMES

Hospices Civils De Lyon

pulmonology, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite

Centre De Lutte Contre Le Cancer Eugene Marquis

ONCOLOGIE, Avenue La Bataille Flandre Dunkerque, Cs 44229, Rennes Cedex

Centre Hospitalier Regional Et Universitaire De Brest

radiology oncology, Boulevard Tanguy Prigent, 29200, Brest

Centre Hospitalier Intercommunal Creteil

pneumology, 40 Avenue De Verdun, 94010, Creteil Cedex

Centre Hospitalier Universitaire De Nice

Pneumology, thoracic oncology and intensive respiratory care, 30 Voie Romaine, 06000, Nice

Institut Universitaire Du Cancer Toulouse-Oncopole

ONCOLOGIE, 1 Avenue Irene Joliot Curie, 31100, Toulouse

Centre Hospitalier Universitaire De Lille

Pulmonology and thoracic oncology department, Boulevard Du Professeur Jules Leclercq, 59000, Lille

Hospices Civils De Lyon

ONCOLOGIE, 59 Boulevard Pinel, 69500, Bron

Institut De Cancerologie De Lorraine

ONCOLOGIE, 6 Avenue De Bourgogne, 54500, Vandouvre Les Nancy

Centre Henri Becquerel

ONCOLOGIE, 1 Rue D Amiens, 76000, Rouen

Institut Gustave Roussy

ONCOLOGIE, 114 Rue Edouard Vaillant, 94800, Villejuif

Centre Oscar Lambret

ONCOLOGIE, 3 Rue Frederic Combemale, 59000, Lille

Centre Antoine Lacassagne

Specialist in Oncology and Radiotherapy, 33 Avenue De Valombrose, 06189, Nice Cedex 2

Centr Georges Francois Leclerc

Radiotherapy Department, 1 Rue Professeur Marion, 21000, Dijon

Hospices Civils De Lyon

pulmonology, 103 Grande Rue De La Croix Rousse, 69317, Lyon Cedex 04

Centre Francois Baclesse

ONCOLOGIE, 3 Avenue Du General Harris, Cs 45026, Caen Cedex 5

Groupe Hospitalier Public Du De L Oise

ONCOLOGIE, 67 Boulevard Laennec, Bp 70072, Creil Cedex

Institut Curie

ONCOLOGIE, 35 Rue Dailly, 92210, Saint-Cloud

Country notifications

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

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
France	2025-03-06		2025-09-09

Results and documents

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

Documents 24 files

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

Type	Title	Version
Protocol (for publication)	D1_Protocol_2023-503326-39-00_OliGRAIL	3.2
Protocol (for publication)	D4_Patient facing document__Fiche PRL SELLES	2
Protocol (for publication)	D4_Patient facing document_Patient Diary	1.1
Protocol (for publication)	D4_Patient facing document_Procedure prelevement selles	2
Protocol (for publication)	D4_Questionnaire-EQ-5D-5L-FR_2023-503326-39-00_OliGRAIL	1
Protocol (for publication)	D4_Questionnaire-LC13-FR_2023-503326-39-00_OliGRAIL	1
Protocol (for publication)	D4_Questionnaire-QLQ-C30-FR_2023-503326-39-00_OliGRAIL	3.0
Recruitment arrangements (for publication)	K1_Recruitment and Informed consent procedure_2023-503326-39-00_OliGRAIL	2.0
Recruitment arrangements (for publication)	K2_CTIS Document additionnel_2023-503326-39-00_OliGRAIL	1
Subject information and informed consent form (for publication)	L1_ICF_2023-503326-39-00_OliGRAIL	3.1
Subject information and informed consent form (for publication)	L1_Lettre d information patients inclus dans l etude	1.0
Subject information and informed consent form (for publication)	L1_SIS_2023-503326-39-00_OliGRAIL	3.1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_IMFINZI	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_IMJUDO	1
Summary of Product Characteristics (SmPC) (for publication)	G2_ SmPC Pembrolizumab	1
Summary of Product Characteristics (SmPC) (for publication)	G2_RCP Pemetrexed solution	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC Carboplatine	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC Cemiplimab	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC Ipilimumab	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC Nivolumab	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC Paclitaxel	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC Tecentriq	1
Summary of Product Characteristics (SmPC) (for publication)	GR2_SmPC Cisplatin	1
Synopsis of the protocol (for publication)	D1_Synopsis-FR_2023-503326-39-00_OliGRAIL	3.2

Application history

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

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-08-09	France	Acceptable 2024-11-19	2024-11-19
2	SUBSTANTIAL MODIFICATION	SM-1	2025-06-17	France	Acceptable 2025-07-23	2025-08-26
3	SUBSTANTIAL MODIFICATION	SM-2	2025-12-09	France	Acceptable 2026-04-07	2026-04-09