A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure

Phase 3

Active, not recruiting

• Conditions: Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: Amivantamab; Drug: Lazertinib; Drug: Pemetrexed; Drug: Carboplatin

• Registration Number: NCT04988295
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-30
• Study First Submitted QC: 2021-07-30
• Study First Posted: 2021-08-03
• Study Start: 2021-11-17
• Primary Completion: 2023-07-10
• Disposition First Posted: 2024-06-20
• Disposition First Submitted: 2024-07-05
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-13
• Last Update Posted: 2024-08-14
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 776

Inclusion Criteria

• Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated
• Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after the time of locally advanced or metastatic disease diagnosis by either epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation
• A participant with a history of brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization and the participant can be receiving no greater than10 milligrams (mg) prednisone or equivalent daily for the treatment of intracranial disease
• Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
• Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <= 2 peripheral neuropathy, or Grade <= 2 hypothyroidism stable on hormone replacement)
• A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
• Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second- line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Participants who received either neoadjuvant and/or adjuvant treatment of any type are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting. Treatment with osimertinib must be discontinued at least 8 days (4 half-lives) prior to randomization (that is last dose no later than Day -8)

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Exclusion Criteria

• Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization
• Participant with symptomatic or progressive brain metastases
• Participant has history of or current evidence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
• Participant has known small cell transformation
• Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
• Participant has a history of clinically significant cardiovascular disease including, but not limited to diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to randomization; myocardial infarction; unstable angina; stroke; transient ischemic attack; coronary/peripheral artery bypass graft; or acute coronary syndrome. Participant has a significant genetic predisposition to venous thromboembolic events. Participant has a prior history of venous thromboembolic events and is not on appropriate therapeutic anticoagulation as per National Comprehensive Cancer Network or local guidelines

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)	Amivantamab	Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)	Pemetrexed	Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
Arm A: LACP/ACP-L	Lazertinib	LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
Arm A: LACP/ACP-L	Pemetrexed	LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
Arm A: LACP/ACP-L	Carboplatin	LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
Arm B: CP (Carboplatin and Pemetrexed)	Pemetrexed	Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.
Arm B: CP (Carboplatin and Pemetrexed)	Carboplatin	Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)	Carboplatin	Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
Arm A2 (Extension Cohort): ACP-L	Lazertinib	Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
Arm A2 (Extension Cohort): ACP-L	Pemetrexed	Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
Arm A2 (Extension Cohort): ACP-L	Carboplatin	Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
Arm C2 (Extension Cohort): ACP	Pemetrexed	Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
Arm C2 (Extension Cohort): ACP	Carboplatin	Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
Arm C2 (Extension Cohort): ACP	Amivantamab	Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
Arm A: LACP/ACP-L	Amivantamab	LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
Arm A2 (Extension Cohort): ACP-L	Amivantamab	Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) According to RECIST v1.1 Guidelines as Assessed by Blinded Independent Central Review (BICR)	Up to approximately 28 months	PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to approximately 48 months	Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.
Serum Concentration of Amivantamab	Up to approximately 28 months	Serum samples will be analyzed to determine concentrations of amivantamab.
Objective Response as Assessed by BICR	Up to approximately 28 months	Objective response is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as their best response as defined by BICR using RECIST v1.1 criteria.
Intracranial PFS	Up to approximately 28 months	Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1.
Time to Symptomatic Progression (TTSP)	Up to approximately 28 months	TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms or death.
Number of Participants with Anti-Amivantamab Antibodies	Up to approximately 28 months	Number of participants with anti-amivantamab antibodies will be reported.
Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)	Up to approximately 28 months	NSCLC-SAQ is a 7-item PRO measure designed for use in adults to assess symptoms of advanced non-small cell lung cancer (NSCLC). The NSCLC-SAQ has a seven-day recall period. It contains five domains and accompanying items that will be identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1 item), fatigue (2 items), and appetite (1 item). Each item uses a response scale between 0 to 4, with higher scores indicating more severe symptomatology. All five of these domains must be non-missing to compute a total score, with a response range from 0 to 20 with higher scores indicating more severe symptomatology.
Duration of Response (DoR)	Up to approximately 28 months	DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR.
Time to Subsequent Therapy (TTST)	Up to approximately 28 months	TTST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death whichever comes first.
Time to Intracranial Disease Progression as Assessed by BICR	Up to approximately 28 months	Time to intracranial disease progression is defined as the time from randomization until the date of objective intracranial disease progression, based on BICR using RECIST v1.1.
Number of Participants with Adverse Events (AEs)	Up to'approximately 48 months	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)	Up to approximately 28 months	PROMIS-PF is used to characterize and better understand overall health, level of physical disability, and general well-being. Physical function is a foundation for commonly used general and cancer-specific patient reported outcomes (PRO) measures.
Progression-Free Survival After First Subsequent Therapy (PFS2)	Up to approximately 28 months	PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.
Intracranial Objective Response Rate (ORR) as Assessed by BICR	Up to approximately 28 months	Intracranial ORR is defined as the percentage of participants who achieve either an intracranial CR or PR, as defined by BICR using RECIST v1.1.
Intracranial Duration of Response (DOR) as Assessed by BICR	Up to approximately 28 months	Intracranial DoR is defined as the time from the date of first documented intracranial response (PR or CR) until the date of documented intracranial progression or death, whichever comes first, for participants who have intracranial CR or PR.
Number of Participants with Clinical Laboratory Abnormalities	Up to approximately 48 months	Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urinalysis) will be reported.
Plasma Concentration of Lazertinib	Up to approximately 28 months	Plasma samples will be analyzed to determine concentrations of lazertinib.
European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score	Up to approximately 28 months	The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.

Trial Locations

Locations (247)

VUMC Amsterdam; 🇳🇱 Amsterdam, Netherlands

Instituto Nacional de Cancerologia; 🇲🇽 Mexico, Mexico

Oncologia Integral Satelite; 🇲🇽 Naucalpan, Mexico

Ziekenhuis St Jansdal; 🇳🇱 Harderwijk, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Centrum Onkologii im. Prof. F. Lukaszczyka; 🇵🇱 Bydgoszcz, Poland

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdansk, Poland

The Second Affiliated Hospital of Zhejiang University College of Medicine; 🇨🇳 Hangzhou, China

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, China

Harbin medical university cancer hospital; 🇨🇳 Harbin, China

Zhejiang Cancer Hospital; 🇨🇳 Hang Zhou, China

Second Affiliated Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, China

Huizhou Municipal Central Hospital; 🇨🇳 Huizhou, China

Taizhou Hospital of Zhejiang Province; 🇨🇳 Linhai, China

Affiliated Hospital of North Sichuan Medical College; 🇨🇳 Nanchong, China

Ruijin Hospital Shanghai Jiao Tong University; 🇨🇳 Shanghai, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China

Shanghai East Hospital; 🇨🇳 Shanghai, China

Oncologianova GmbH; 🇩🇪 Recklinghausen, Germany

Universitaetsklinikum Regensburg; 🇩🇪 Regensburg, Germany

Health Care Global Enterprises pvt Ltd; 🇮🇳 Bangalore, India

Artemis Hospital; 🇮🇳 Gurugram, India

Ospedale S. Maria Delle Croci; 🇮🇹 Ravenna, Italy

Istituto Nazionale Tumori Regina Elena; 🇮🇹 Roma, Italy

Policlinico G.B.Rossi; 🇮🇹 Verona, Italy

National Hospital Organization Shibukawa Medical Center; 🇯🇵 Gunma, Japan

Hyogo Cancer Center; 🇯🇵 Hyogo, Japan

Kanagawa Cancer Center; 🇯🇵 Kanagawa, Japan

Health Pharma Professional Research; 🇲🇽 Mexico, Mexico

Szpitale Pomorskie Sp z o o; 🇵🇱 Gdynia, Poland

Warminsko-Mazurskie Centrum Chorob Pluc w Olsztynie; 🇵🇱 Olsztyn, Poland

Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandow; 🇵🇱 Poznan, Poland

Private Specialist Hospitals - MedPolonia; 🇵🇱 Poznan, Poland

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy; 🇵🇱 Warszawa, Poland

Hosp. Univ. I Politecni La Fe; 🇪🇸 Valencia, Spain

Clinica Univ. de Navarra; 🇪🇸 Pamplona, Spain

Sahlgrenska Universitetssjukhuset; 🇸🇪 Goteborg, Sweden

Hosp. Virgen Del Rocio; 🇪🇸 Seville, Spain

Linkoping University Hospital; 🇸🇪 Linkoping, Sweden

Hosp. Gral. Univ. Valencia; 🇪🇸 Valencia, Spain

Skanes universitetssjukhus; 🇸🇪 Lund, Sweden

Norrlands Universitetssjukhus; 🇸🇪 Umea, Sweden

Akademiska Sjukhuset; 🇸🇪 Uppsala, Sweden

Changhua Christian Hospital; 🇨🇳 Changhua, Taiwan

The First Affiliated Hospital Sun Yat sen University; 🇨🇳 Guang Zhou, China

Sun Yat-Sen Memorial Hospital Sun Yat-sen University; 🇨🇳 Guangzhou, China

Texas Oncology Baylor Charles A Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

Hosp Univ A Coruna; 🇪🇸 A Coruña, Spain

Hosp Regional Univ de Malaga; 🇪🇸 Málaga, Spain

Guys and St Thomas NHS Foundation Trust; 🇬🇧 London, United Kingdom

Southern Cancer Center, PC; 🇺🇸 Mobile, Alabama, United States

Arizona Oncology Associates; 🇺🇸 Tucson, Arizona, United States

City of Hope; 🇺🇸 Duarte, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

University of California Irvine; 🇺🇸 Orange, California, United States

Rocky Mountain Cancer Centers; 🇺🇸 Colorado Springs, Colorado, United States

Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center; 🇺🇸 Fort Lauderdale, Florida, United States

University Cancer And Blood Center LLC; 🇺🇸 Athens, Georgia, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Nebraska Cancer Specialists; 🇺🇸 Grand Island, Nebraska, United States

Astera Cancer Care; 🇺🇸 East Brunswick, New Jersey, United States

TriHealth Network; 🇺🇸 Cincinnati, Ohio, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Kaiser Permanente Northwest; 🇺🇸 Portland, Oregon, United States

Alliance Cancer Specialists; 🇺🇸 Horsham, Pennsylvania, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Fundação São Francisco Xavier; 🇧🇷 Ipatinga, Brazil

Baptist Cancer Center; 🇺🇸 Memphis, Tennessee, United States

Texas Oncology-Medical City Dallas; 🇺🇸 Dallas, Texas, United States

Texas Oncology; 🇺🇸 Grapevine, Texas, United States

Oncology Consultants - Texas; 🇺🇸 Houston, Texas, United States

Texas Oncology - Northeast; 🇺🇸 Longview, Texas, United States

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Blue Ridge Cancer Care; 🇺🇸 Wytheville, Virginia, United States

NorthWest Medical Specialties, PLLC; 🇺🇸 Puyallup, Washington, United States

Compass Oncology; 🇺🇸 Vancouver, Washington, United States

CINME Centro de Investigaciones Metabolicas; 🇦🇷 Caba, Argentina

IADT Instituto Argentino de Diagnostico y Tratamiento; 🇦🇷 Caba, Argentina

Centro Medico Fleischer; 🇦🇷 Caba, Argentina

CEMIC (Centro de Educación Médica e Investigaciones Clínicas); 🇦🇷 Caba, Argentina

Hospital Privado Universitario De Cordoba; 🇦🇷 Cordoba, Argentina

Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica; 🇦🇷 Córdoba, Argentina

Hospital Privado de la Comunidad; 🇦🇷 Mar del Plata, Argentina

Clínica Viedma; 🇦🇷 Viedma, Argentina

Grand Hopital de Charleroi, site Notre Dame; 🇧🇪 Charleroi, Belgium

UZA; 🇧🇪 Edegem, Belgium

UZ Gent; 🇧🇪 Gent, Belgium

Jessa Ziekenhuis - Campus Virga Jesse; 🇧🇪 Hasselt, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

CHU Sart-Tilman; 🇧🇪 Liege, Belgium

Clinique Saint Pierre; 🇧🇪 Ottignies, Belgium

Cetus Oncologia; 🇧🇷 Belo Horizonte, Brazil

CIONC Centro Integrado de Oncologia de Curitiba; 🇧🇷 Curitiba, Brazil

Ynova Pesquisa Clinica; 🇧🇷 Florianopolis, Brazil

UPCO Unidade de Pesquisa Clinica em Oncologia; 🇧🇷 Pelotas, Brazil

Associacao Hospitalar Moinhos de Vento; 🇧🇷 Porto Alegre, Brazil

Hospital Ernesto Dornelles; 🇧🇷 Porto Alegre, Brazil

Oncoclinicas Rio de Janeiro S A; 🇧🇷 Rio de Janeiro, Brazil

Instituto D Or de Pesquisa e Ensino IDOR; 🇧🇷 Rio de Janeiro, Brazil

Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI); 🇧🇷 Rio de Janeiro, Brazil

Nucleo de Oncologia da Bahia; 🇧🇷 Salvador, Brazil

Hospital Sao Rafael; 🇧🇷 Salvador, Brazil

CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia; 🇧🇷 Santo Andre, Brazil

Real e Benemerita Associacao Portuguesa de Beneficencia; 🇧🇷 Sao Paulo, Brazil

Hospital Paulistano; 🇧🇷 Sao Paulo, Brazil

Hospital Alemao Oswaldo Cruz; 🇧🇷 Sao Paulo, Brazil

Fundacao Antonio Prudente A C Camargo Cancer Center; 🇧🇷 Sao Paulo, Brazil

Onco Star SP Oncologia Ltda; 🇧🇷 Sao Paulo, Brazil

IOS - Instituto de Oncologia de Sorocaba Dr. Gilson Delgado; 🇧🇷 Sorocaba, Brazil

Hospital Nove de Julho; 🇧🇷 São Paulo, Brazil

COT - Centro Oncologico do Triangulo S.A; 🇧🇷 Uberlandia, Brazil

Multifunctional Hospital for Active Treatment 'Serdika'; 🇧🇬 Sofia, Bulgaria

Multiprofile Hospital for Active Treatment 'Tokuda Hospital Sofia'; 🇧🇬 Sofia, Bulgaria

Specialized Hospital for Active Treatment in Oncology; 🇧🇬 Sofia, Bulgaria

UMHAT Sofia Med; 🇧🇬 Sofia, Bulgaria

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

British Columbia Cancer Agency; 🇨🇦 Vancouver, British Columbia, Canada

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

Cancer Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, China

Peking University People s Hospital; 🇨🇳 Beijing, China

Beijing Cancer Hospital; 🇨🇳 Beijing, China

Chinese PLA General Hospital; 🇨🇳 Beijing, China

Evangelische Lungenklinik Berlin; 🇩🇪 Berlin, Germany

Beijing Chest hospital, Capital medical university; 🇨🇳 Beijing, China

Hunan Cancer hospital; 🇨🇳 Changsha, China

Sichuan Cancer Hospital; 🇨🇳 Chengdu, China

West China Hospital Sichuan University; 🇨🇳 Chengdu, China

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, China

Southwest Hospital; 🇨🇳 ChongQing, China

Shenzhen university General Hospital; 🇨🇳 Shenzhen, China

Cancer Hospital Chinese Academy of Medical Sciences; 🇨🇳 Shenzhen, China

Tianjin Medical University General Hospital; 🇨🇳 Tianjin, China

Weifang People's Hospital; 🇨🇳 Weifang, China

The First Affiliated Hospital of Xian Jiaotong University; 🇨🇳 XI An, China

Yantai Yuhuangding Hospital; 🇨🇳 Yantai, China

Daping Hospital Army Characteristic Medical Center; 🇨🇳 Yuzhong District, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, China

Fakultni nemocnice Olomouc - I.P.Pavlova 6; 🇨🇿 Olomouc, Czechia

Vitkovicka nemocnice a.s.; 🇨🇿 Ostrava- Vitkovice, Czechia

Fakultni nemocnice Plzen; 🇨🇿 Plzen, Czechia

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Institut Sainte Catherine; 🇫🇷 Avignon Cedex 9, France

Hospices Civils de Lyon HCL; 🇫🇷 Bron, France

CHU de Grenoble Hopital Albert Michallon; 🇫🇷 La Tronche, France

Centre Hospitalier du Mans; 🇫🇷 le Mans, France

CHR Hôpital Calmette; 🇫🇷 Lille, France

Hopital Nord; 🇫🇷 Marseille Cedex 20, France

CHU de Montpellier - Arnaud de Villeneuve; 🇫🇷 Montpellier Cedex 5, France

Institut Curie; 🇫🇷 Paris, France

CHU Bordeaux; 🇫🇷 Pessac, France

CHRU Hopital de Pontchaillou; 🇫🇷 Rennes, France

CHU Nantes; 🇫🇷 Sain-Herblain, France

Nouvel Hopital Civil - CHU Strasbourg; 🇫🇷 Strasbourg cedex, France

CHU Bretonneau; 🇫🇷 Tours, France

Asklepios Klinikum Harburg; 🇩🇪 Hamburg, Germany

Thoraxklinik am Universitatsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Onkologische Schwerpunktpraxis; 🇩🇪 Heilbronn, Germany

POIS Sachsen GmbH iG; 🇩🇪 Leipzig, Germany

Bethanien Krankenhaus; 🇩🇪 Moers, Germany

Klinikum der Universitaet Muenchen; 🇩🇪 München, Germany

Tata Medical Center; 🇮🇳 Kolkata, India

Tata Memorial Hospital; 🇮🇳 Mumbai, India

HCG Manavta Cancer Centre; 🇮🇳 Nasik, India

Rajiv Gandhi Cancer Institute and Research Centre; 🇮🇳 New Delh, India

Noble Hospital Pvt Ltd; 🇮🇳 Pune, India

Bhaktivedanta Hospital & Research Institute; 🇮🇳 Thane, India

Soroka University Medical Center; 🇮🇱 Beersheba, Israel

Rambam Health Corporation; 🇮🇱 Haifa, Israel

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel

Meir Medical Center; 🇮🇱 Kfar Saba, Israel

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

Chaim Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Tel-Aviv Sourasky Medical Center; 🇮🇱 Tel-Aviv, Israel

CRO IRCCS Istituto Nazionale Tumori; 🇮🇹 Aviano, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori; 🇮🇹 Meldola, Italy

Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

Azienda Ospedaliero-Universitaria Di Parma; 🇮🇹 Parma, Italy

Kobe City Medical Center General Hospital; 🇯🇵 Kobe City, Japan

Kurume University Hospital; 🇯🇵 Kurume, Japan

National Hospital Organization Nagoya Medical Center; 🇯🇵 Nagoya-shi, Japan

Niigata Cancer Center Hospital; 🇯🇵 Niigata, Japan

Osaka International Cancer Institute; 🇯🇵 Osaka City, Japan

Shizuoka Cancer Center; 🇯🇵 Shizuoka, Japan

Llc, Eurocityclinic; 🇷🇺 Saint Petersburg, Russian Federation

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital; 🇯🇵 Tokyo, Japan

The Cancer Institute Hospital of JFCR; 🇯🇵 Tokyo, Japan

Ehime University Hospital; 🇯🇵 Toon-shi, Japan

Wakayama Medical University Hospital; 🇯🇵 Wakayama, Japan

National Hospital Organization Iwakuni Clinical Center; 🇯🇵 Yamaguchi, Japan

National Hospital Organization Yamaguchi Ube Medical Center; 🇯🇵 Yamaguchi, Japan

National Cancer Center; 🇰🇷 Gyeonggi-do, Korea, Republic of

CHA Bundang Medical Center, CHA University; 🇰🇷 Gyeonggi-do, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Gyeonggi-do, Korea, Republic of

GyeongSang National University Hospital; 🇰🇷 Gyeongsangnam-do, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea Seoul St Mary s Hospital; 🇰🇷 Seoul, Korea, Republic of

University Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia

Hospital Tengku Ampuan Afzan; 🇲🇾 Kuantan, Malaysia

Beacon Hospital Sdn Bhd; 🇲🇾 Petaling Jaya, Malaysia

Subang Jaya Medical Centre; 🇲🇾 Subang Jaya, Malaysia

Mount Miriam Cancer Hospital; 🇲🇾 Tanjung Bungah, Malaysia

Hospital Civil de Guadalajara Fray Antonio Alcalde; 🇲🇽 Guadalajara, Mexico

CIMOVA, Morals Vargas Centro de Investigación SC; 🇲🇽 Leon, Mexico

Centro Hospitalar Lisboa Norte EPE - Hospital Pulido Valente; 🇵🇹 Lisboa, Portugal

Hospital Beatriz Angelo; 🇵🇹 Loures, Portugal

Centro Hospitalar Universitario do Porto, EPE; 🇵🇹 Porto, Portugal

Instituto Portugues de Oncologia; 🇵🇹 Porto, Portugal

Pan American Center for Oncology Trials LLC; 🇵🇷 Rio Piedras, Puerto Rico

City Clinical Hospital #1; 🇷🇺 Nalchik, Russian Federation

Hosp. de La Santa Creu I Sant Pau; 🇪🇸 Barcelona, Spain

Hosp. Univ. Quiron Dexeus; 🇪🇸 Barcelona, Spain

Hosp Univ Vall D Hebron; 🇪🇸 Barcelona, Spain

Hosp Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hosp. Univ. Insular de Gran Canaria; 🇪🇸 Las Palmas de Gran Canaria, Spain

Hosp. Gral. Univ. Gregorio Maranon; 🇪🇸 Madrid, Spain

Hosp Univ Fund Jimenez Diaz; 🇪🇸 Madrid, Spain

Hosp. Univ. 12 de Octubre; 🇪🇸 Madrid, Spain

Hosp. Univ. La Paz; 🇪🇸 Madrid, Spain

Hosp Univ Hm Sanchinarro; 🇪🇸 Madrid, Spain

Hosp. Univ. Pta. de Hierro Majadahonda; 🇪🇸 Majadahonda, Spain

Kaohsiung Medical University Chung Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Taipei Medical University Shuang Ho Hospital; 🇨🇳 New Taipei City, Taiwan

Chung Shan Medical University Hospital; 🇨🇳 Taichung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Adana City Hospital; 🇹🇷 Adana, Turkey

Memorial Ankara Hastanesi; 🇹🇷 Ankara, Turkey

Gazi University Hospital; 🇹🇷 Ankara, Turkey

Ankara Bilkent City Hospital; 🇹🇷 Ankara, Turkey

Trakya University Medical Faculty; 🇹🇷 Edirne, Turkey

Istanbul University Cerrahpasa Medical Faculty; 🇹🇷 Istanbul, Turkey

Bakirkoy Training and Research Hospital; 🇹🇷 Istanbul, Turkey

Medipol Mega University Hospital; 🇹🇷 Istanbul, Turkey

Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi; 🇹🇷 Istanbul, Turkey

Medical Point; 🇹🇷 Izmir, Turkey

Velindre Hospital; 🇬🇧 Cardiff, United Kingdom

Edinburgh Cancer Centre Western General; 🇬🇧 Edinburgh, United Kingdom

UCL Cancer Institute; 🇬🇧 London, United Kingdom

The Royal Marsden NHS Trust; 🇬🇧 London, United Kingdom

The Christie Nhs Foundation Trust; 🇬🇧 Manchester, United Kingdom

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong