JOURNAL ONKOLOGIE – STUDIE

REZILIENT3

A Study of Zipalertinib and Chemotherapy Compared With Chemotherapy Alone in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion.

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05973773

Studienbeginn:
Juni 2023

Letztes Update:
03.04.2024

Wirkstoff:
TAS6417

Indikation (Clinical Trials):
Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Taiho Oncology, Inc.

Collaborator:
-

Kontakt

Taiho Oncology, INC
Kontakt:
Phone: 609-250-7336
E-Mail: clinicaltrialinfo@taihooncology.com» Kontaktdaten anzeigen

Studienlocations
(3 von 82)

Universitätsklinikum Gießen und Marburg - Gießen
35392 Gießen
(Hessen)
GermanyNoch nicht rekrutierend» Google-Maps

LMU Klinikum - Campus Innenstadt
80337 München
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps

Pankreaskarzinomzentrum Universitätsklinikum Regensburg
Franz-Josef-Strauß-Allee 11
93053 Regensburg
DeutschlandNoch nicht rekrutierend» Google-Maps

Comprehensive Cancer Centers of Nevada - Henderson
89052 Henderson
United StatesRekrutierend» Google-Maps

Comprehensive Cancer Centers of Nevada - Horizon Ridge Henderson
89052 Henderson
United StatesRekrutierend» Google-Maps

Comprehensive Cancer Centers of Nevada - Southeast Henderson - Stephanie
89074 Henderson
United StatesRekrutierend» Google-Maps

Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II
89144 Las Vegas
United StatesRekrutierend» Google-Maps

Comprehensive Cancer Centers of Nevada - Southwest
89148 Las Vegas
United StatesRekrutierend» Google-Maps

Comprehensive Cancer Centers of Nevada - Central Valley - Twain
89169 Las Vegas
United StatesRekrutierend» Google-Maps

Comprehensive Cancer Centers of Nevada - Northwest
89218 Las Vegas
United StatesRekrutierend» Google-Maps

Gabrail Cancer and Research Center
44718 Canton
United StatesRekrutierend» Google-Maps

Universitair Ziekenhuis Leuven - Campus Gasthuisberg
3000 Leuven
BelgiumNoch nicht rekrutierend» Google-Maps

Algemeen Ziekenhuis Maria Middelares
9000 Gent
BelgiumNoch nicht rekrutierend» Google-Maps

Algemeen Ziekenhuis Delta - Campus Rumbeke
8800 Rosières
BelgiumRekrutierend» Google-Maps

William Osler Health System - Brampton Civic Hospital
L6R 3J7 Brampton
CanadaNoch nicht rekrutierend» Google-Maps

Princess Margaret Cancer Centre
M5G 2M9 Toronto
CanadaNoch nicht rekrutierend» Google-Maps

Les Hôpitaux Universitaires de Strasbourg
67091 Strasbourg cedex
FranceNoch nicht rekrutierend» Google-Maps

Hôpital Côte De Nacre
14033 Caen cedex 9
FranceNoch nicht rekrutierend» Google-Maps

Institut Curie
75248 Paris cedex
FranceNoch nicht rekrutierend» Google-Maps

Centre Hospitalier Universitaire Limoges
87042 Limoges
FranceNoch nicht rekrutierend» Google-Maps

Hôpital Haut-Lévêque
33604 Pessac
FranceNoch nicht rekrutierend» Google-Maps

Centre Hospitalier Le Mans
72037 Le Mans cedex 9
FranceNoch nicht rekrutierend» Google-Maps

Hôpital Ambroise-Paré
92100 Boulogne-Billancourt
FranceNoch nicht rekrutierend» Google-Maps

Shaare Zedek Medical Center
9103102 Jerusalem
IsraelNoch nicht rekrutierend» Google-Maps

Hadassah University Hospital Ein Kerem
9112001 Jerusalem
IsraelNoch nicht rekrutierend» Google-Maps

Tel Aviv Sourasky Medical Center
6423906 Tel Aviv
IsraelNoch nicht rekrutierend» Google-Maps

Assuta Hospital - Ramat HaHayal
69710 Tel aviv
IsraelNoch nicht rekrutierend» Google-Maps

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST
47014 Meldola
ItalyNoch nicht rekrutierend» Google-Maps

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
20132 Milan
ItalyNoch nicht rekrutierend» Google-Maps

Azienda Ospedaliero - Universitaria di Modena
41224 Modena
ItalyNoch nicht rekrutierend» Google-Maps

Fondazione IRCCS Policlinico San Matteo
27100 Pavia
ItalyNoch nicht rekrutierend» Google-Maps

Azienda Unità Sanitaria Locale della Romagna
48121 Ravenna
ItalyNoch nicht rekrutierend» Google-Maps

Azienda Ospedaliera Universitaria Integrata Verona
37126 Verona
ItalyNoch nicht rekrutierend» Google-Maps

Aichi Cancer Center
464-8681 Nagoya
JapanRekrutierend» Google-Maps

Hirosaki University Hospital
036-8563 Hirosaki-Shi
JapanRekrutierend» Google-Maps

Kyushu Cancer Center
811-1395 Fukuoka-shi
JapanRekrutierend» Google-Maps

Kitasato University Hospital
252-0375 Sagamihara
JapanRekrutierend» Google-Maps

Kanagawa Cardiovascular and Respiratory Center
236-0051 Yokohama
JapanRekrutierend» Google-Maps

Saiseikai Kumamoto Hospital
861-4163 Kumamoto-Shi
JapanRekrutierend» Google-Maps

Sendai Kousei Hospital
980-0873 Sendai
JapanRekrutierend» Google-Maps

Okayama University Hospital
700-8558 Okayamashi
JapanRekrutierend» Google-Maps

Kansai Medical University Hospital
573-1191 Hirakata
JapanRekrutierend» Google-Maps

National Hospital Organization Kinki-Chuo Chest Medical Center
591-8555 Sakai-Shi
JapanRekrutierend» Google-Maps

Cancer Institute Hospital of JFCR
135-8550 Koto
JapanRekrutierend» Google-Maps

Keio University Hospital
160-8582 Shinjuku-Ku
JapanNoch nicht rekrutierend» Google-Maps

Kanazawa University Hospital
920-8641 Kanazawa
JapanRekrutierend» Google-Maps

Osaka City General Hospital
534-0021 Osaka
JapanRekrutierend» Google-Maps

Osaka Prefectural Hospital Organization - Osaka International Cancer Institute
541-8567 Osaka
JapanRekrutierend» Google-Maps

Catholic University of Korea Saint Vincent's Hospital
16247 Suwon-si
Korea, Republic ofNoch nicht rekrutierend» Google-Maps

Ajou University Hospital
16499 Suwon-si
Korea, Republic ofNoch nicht rekrutierend» Google-Maps

Gyeongsang National University Hospital
52727 Jinju
Korea, Republic ofNoch nicht rekrutierend» Google-Maps

Inha University Hospital
22332 Incheon
Korea, Republic ofNoch nicht rekrutierend» Google-Maps

Korea University Anam Hospital
02841 Seoul
Korea, Republic ofNoch nicht rekrutierend» Google-Maps

Korea University Guro Hospital
08308 Seoul
Korea, Republic ofNoch nicht rekrutierend» Google-Maps

Radboud Universitair Medisch Centrum
6525 GA Nijmegen
NetherlandsNoch nicht rekrutierend» Google-Maps

Vrije Universiteit Medisch Centrum
1081 HV Amsterdam
NetherlandsRekrutierend» Google-Maps

St. Luke's Medical Center - Quezon City
1112 Quezon City
PhilippinesNoch nicht rekrutierend» Google-Maps

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
20-954 Lublin
PolandNoch nicht rekrutierend» Google-Maps

Instytut MSF
90-302 Łódź
PolandNoch nicht rekrutierend» Google-Maps

Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandów
60-569 Pozna?
PolandNoch nicht rekrutierend» Google-Maps

Tan Tock Seng Hospital
30433 Singapore
SingaporeNoch nicht rekrutierend» Google-Maps

Complejo Hospitalario Universitario A Coruña
15006 A Coruña
SpainNoch nicht rekrutierend» Google-Maps

Clínica Mi Tres Torres
08017 Barcelona
SpainRekrutierend» Google-Maps

Hospital Quirónsalud Barcelona
08023 Barcelona
SpainRekrutierend» Google-Maps

Hospital Clinic de Barcelona
08036 Barcelona
SpainNoch nicht rekrutierend» Google-Maps

Hospital Universitario de Jaén
23007 Jaén
SpainRekrutierend» Google-Maps

MD Anderson Cancer Center Madrid
28033 Madrid
SpainNoch nicht rekrutierend» Google-Maps

Hospital Universitario Fundación Jiménez Díaz
28040 Madrid
SpainNoch nicht rekrutierend» Google-Maps

Hospital Universitario 12 de Octubre
28041 Madrid
SpainNoch nicht rekrutierend» Google-Maps

Hospital Universitario La Paz
28046 Madrid
SpainRekrutierend» Google-Maps

Hospital Regional Universitario de Málaga - Hospital General
29010 Málaga
SpainNoch nicht rekrutierend» Google-Maps

Torbay and South Devon NHS Foundation Trust
TQ2 7AA Torquay
TurkeyNoch nicht rekrutierend» Google-Maps

T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastanesi
01060 Adana
TurkeyNoch nicht rekrutierend» Google-Maps

Medical Park Seyhan Hastanesi
01120 Adana
TurkeyNoch nicht rekrutierend» Google-Maps

Memorial Ankara Hastanesi
6520 Ankara
TurkeyNoch nicht rekrutierend» Google-Maps

Trakya Üniversitesi Sa?l?k Ara?t?rma ve Uygulama Merkezi
22130 Edirne
TurkeyNoch nicht rekrutierend» Google-Maps

Ankara Il Saglik Mudurlugu SBU Gulhane Egitim Ve Arastirma Hastanesi
06010 Etlik
TurkeyNoch nicht rekrutierend» Google-Maps

Bagcilar Medipol Mega Universite Hastanesi
34214 Istanbul
TurkeyNoch nicht rekrutierend» Google-Maps

T.C. Saglik Bakanligi - Istanbul Il Saglik Mudurlugu - Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
34722 Istanbul
TurkeyNoch nicht rekrutierend» Google-Maps

T.C. Saglik Bakanligi Ankara Bilkent Sehi?r Hastanesi?
06800 Çankaya
TurkeyNoch nicht rekrutierend» Google-Maps

Royal Free London NHS Foundation Trust
NW3 2QG London
United KingdomNoch nicht rekrutierend» Google-Maps

Nottingham University Hospitals NHS Trust
NG5 1PB Nottingham
United KingdomNoch nicht rekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Detailed Description:

This study will evaluate the efficacy and safety of zipalertinib in combination with standard

chemotherapy with pemetrexed and a platinum agent (either carboplatin or cisplatin) in

patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC

harboring EGFR ex20ins mutations.

The study will be conducted in two parts:

- Part A: Safety lead-in to determine the recommended dose of zipalertinib in combination

with standard chemotherapy pemetrexed and a platinum agent (either carboplatin or

cisplatin) to be studied in Part B of the study.

- Part B: Randomized, controlled, open-label, multinational Phase 3 study to assess the

efficacy and safety of zipalertinib in combination with standard chemotherapy with

pemetrexed and a platinum agent (either carboplatin or cisplatin) compared to standard

chemotherapy alone. An independent data monitoring committee (IDMC) will be established

to monitor interim safety Data.

A treatment cycle is defined as 21 days for both parts of the study.

Part A: Safety Lead-In The primary objective of Part A is to determine the recommended dose

of zipalertinib administered in combination with pemetrexed and a platinum agent (either

carboplatin or cisplatin) to be studied in the Phase 3 portion of this study.

Approximately 6-12 patients will receive zipalertinib administered at an initial dose of

zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or

cisplatin on a 21-day cycle. Patients may continue to receive study treatment until

documentation of progressive disease (PD) or until other withdrawal criteria are met,

whichever comes first. Patients will be enrolled using a rolling-6 design,35 and the

determination of the dose of zipalertinib to be used in Part B of the study will be informed

by the incidence of dose-limiting toxicities (DLTs) observed during Cycle 1.

Part B: Phase 3 Enrollment into the Phase 3 portion of the study will begin following

completion of Part A.

Approximately 300 patients will be randomized on a 1:1 basis to receive pemetrexed and a

platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day

cycle.

Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive

zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of

PD or until other withdrawal criteria are met, whichever comes first.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Provide written informed consent.

2. ≥18 years of age (or meets the country's regulatory definition for legal adult age,

whichever is greater).

3. Pathologically confirmed, locally advanced or metastatic nonsquamous NSCLC

4. Has not received any prior systemic treatment for their locally advanced or metastatic

nonsquamous NSCLC. Prior adjuvant/neoadjuvant treatment for advanced or metastatic

disease >6 months prior to first dose of study treatment is allowed for early-stage

NSCLC.

5. Documented EGFR mutation status, as determined by local testing performed at a CLIA

certified or equivalent laboratory, defined as follows:

1. Part A: ex20ins or other common single or compound EGFR mutation

2. Part B: ex20ins EGFR mutation

6. Archival tumor tissue available for submission, with minimum quantity sufficient to

evaluate EGFR mutation status and, where possible, other biomarkers. Patients with

insufficient tissue (details provided in laboratory manual) may be eligible following

discussion with the sponsor; a fresh biopsy will not be required.

7. Patients with previously treated brain metastasis(es) and stable CNS disease (defined

as being neurologically stable and receiving a stable or decreasing corticosteroid

dose at time of enrollment) are eligible.

8. At least one measurable lesion as determined per RECIST 1.1 for patients enrolling to

Part B. Patients enrolling to Part A may be enrolled without measurable disease.

9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.10. Adequate organ

function, as defined by the laboratory value

10. Have a life expectancy of at least 3 months as assessed by the investigator.

11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test

prior to administration of the first dose of study treatment. Female patients are not

considered to be of childbearing potential if they are postmenopausal (no menses for

12 months without an alternative medical cause) or permanently sterile (hysterectomy,

bilateral salpingectomy, or bilateral oophorectomy).

12. Both males and females of reproductive potential must agree to use effective birth

control during the study prior to the first dose and for 6 months after the last dose

of study treatment or longer, based on local requirements.

Exclusion Criteria:

1. Is currently receiving an investigational drug in a clinical trial or participating in

any other type of medical research judged not to be scientifically or medically

compatible with this study.

2. Prior treatment with any of the following within the specific time frame specified:

1. Zipalertinib (TAS6417/CLN-081) at any time.

2. Thoracic radiotherapy ≤28 days, palliative radiation of nonthoracic disease ≤14

days, or palliative radiation of a single lesion ≤7 days prior to first dose of

study treatment.

3. Major surgery (excluding placement of vascular access) ≤28 days prior to first

dose of study treatment.

3. Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment in the

neoadjuvant or adjuvant setting, except for Grade 2 alopecia or skin pigmentation.

4. Patients with other chronic but stable Grade 2 toxicities may be allowed to enroll

after agreement between the investigator and Sponsor.

5. Past medical history of interstitial lung disease, treatment-related pneumonitis (any

grade), or any evidence of clinically active interstitial lung disease.

6. Impaired cardiac function or clinically significant cardiac disease, including any of

the following:

1. History of congestive heart failure (CHF) Class III/IV according to the New York

Heart Association (NYHA) Functional Classification (Appendix A).

2. Serious cardiac arrhythmias requiring treatment.

3. Resting corrected QT interval (QTc) >470 msec calculated using Fridericia's

formula (QTcF).

7. Unable to swallow tablets/capsules or has any disease or condition that may

significantly affect gastrointestinal (GI) absorption of zipalertinib (such as

inflammatory bowel disease, malabsorption syndrome, or prior GI resection). History of

another primary malignancy ≤2 years prior to the date of first dose of study treatment

unless at least one of the following criteria are met:

1. Adequately treated basal or squamous cell carcinoma of the skin

2. Cancer of the breast or cervix in situ

3. Previously treated malignancy, if all treatment for that malignancy was completed

at least 2 years prior to first dose of study treatment, and no current evidence

of disease

4. Concurrent malignancy determined to be clinically stable and not requiring tumor

directed treatment

8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that

is unstable or not controlled with treatment.

9. History of COVID-19 infection within 4 weeks prior to enrolment and/or have

persistent, clinically significant pulmonary symptoms related to prior COVID-19

infection.

10. Active bleeding disorders.

11. Known hypersensitivity to the ingredients in zipalertinib or any drugs similar in

structure or class.

12. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12

supplementation during treatment with pemetrexed.

13. Is pregnant or lactating.

14. The patient is, in the investigator's opinion, unable or unwilling to comply with the

trial procedures.

Studien-Rationale

Primary outcome:

1. Part A and B: The rate and severity of treatment emergent AEs (Time Frame - approximately 5 years)

2. Part A and Part B: Progression-free survival (PFS) by blinded independent central review (BICR) (Time Frame - approximately 5 years)

3. Part A: The rate and severity of DLTs according to the NCI-Common Terminology Criteria of Adverse Events (CTCAE) v5.0 during Cycle 1 (Time Frame - approximately 5 years)

Secondary outcome:

1. Part A and Part B: Objective response rate (ORR) (Time Frame - approximately 5 years)

2. Part A and Part B: Disease control rate (DCR) (Time Frame - approximately 5 years)

3. Part A and Part B: Duration of response (DoR) (Time Frame - approximately 5 years)

4. Part A and Part B: Intracranial (i) Overall Response Rate (iORR) (Time Frame - approximately 5 years)

5. Part A and Part B: Intracranial duration of complete response (iDCR) (Time Frame - approximately 5 years)

6. Part A and Part B: Intracranial duration of Response (iDoR) (Time Frame - approximately 5 years)

7. Part B: Overall survival (OS) (Time Frame - approximately 5 years)

8. Pharmacokinetic (PK) parameter (Time Frame - approximately 5 years):
Minimum observed concentration (Cmin)

9. European Quality of Life 5 Dimensions, 3 Level Version (EQ-5D-3L) (Time Frame - approximately 5 years):
The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. This scale is numbered from 0 to 100. The higher the score the better the outcome

10. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 (Time Frame - approximately 5 years):
The EORTC QLQ-C30 is a "core questionnaire" which incorporates a range of physical, emotional and social health developed to assess the quality of life of cancer patients. This scale is numbered from 30 to 130. The higher the score equates to better functioning.

11. Non-small Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ ) (Time Frame - approximately 5 years):
The NSCLC- SAQ was developed to incorporate the patient's perspective into evaluation of clinical benefit in advanced non-small cell lung cancer trials.. Qualitative evidence supports 7 items covering 5 symptom concepts with the total score measuring overall severity of the following NSCLC symptoms: cough, pain, dyspnea, fatigue, and appetite. Lower scores indicate lower symptom severity.

Studien-Arme

Experimental: Part A (Safety Lead in)
Part A: Safety Lead-In Approximately 6-12 patients will receive zipalertinib administered at an initial dose of zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or cisplatin on a 21-day cycle. Patients may continue to receive study treatment until documentation of progressive disease (PD) or until other withdrawal criteria are met, whichever comes first.
Experimental: Part B
Part B: Phase 3 Enrollment into the Phase 3 portion of the study will begin following completion of Part A. Approximately 300 patients will be randomized on a 1:1 basis to receive pemetrexed and a platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day cycle. Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Geprüfte Regime

TAS6417 (Zipalertinib / CLN-081 / ):
oral tablets/capsules

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

"A Study of Zipalertinib and Chemotherapy Compared With Chemotherapy Alone in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion."

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