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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05967689




Registration number
NCT05967689
Ethics application status
Date submitted
11/07/2023
Date registered
1/08/2023
Date last updated
1/10/2024

Titles & IDs
Public title
A Study of Zipalertinib in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions or Other Uncommon Mutation.
Scientific title
An Open-Label, Phase 2b, Global Multicenter Cohort Trial to Assess the Safety and Efficacy of Zipalertinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Exon 20 Insertion and Uncommon/Single or Compound Epidermal Growth Factor Receptor Mutations.
Secondary ID [1] 0 0
2023-503865-48
Secondary ID [2] 0 0
TAS6417-201
Universal Trial Number (UTN)
Trial acronym
REZILIENT2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TAS6417

Experimental: Cohort A ("prior ex20ins treatment") - Cohort A ("prior ex20ins treatment") participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Experimental: Cohort B ("1st line treatment") - Cohort B participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Experimental: Cohort C ("active brain mets") - Cohort C participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Experimental: Cohort D ("other uncommon EGFRmt"). - Cohort D participants will receive zipalertinib orally twice a day (BID) continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.


Treatment: Drugs: TAS6417
Oral tablets/capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All Cohorts: objective response rate (ORR)
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
All Cohorts: The rate and severity of treatment emergent AEs
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
All Cohorts: Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
All Cohorts: Disease control rate (DCR)
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
All Cohorts: Duration of response (DoR)
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [5] 0 0
Progression-free survival (PFS)
Timepoint [5] 0 0
Up to approximately 2 years
Secondary outcome [6] 0 0
Cohort C: Intracranial (i) Overall Response Rate (iORR)
Timepoint [6] 0 0
Up to approximately 2 years
Secondary outcome [7] 0 0
Cohort C: intracranial duration of complete response (iDCR)
Timepoint [7] 0 0
Up to approximately 2 years
Secondary outcome [8] 0 0
Cohort C: intracranial duration of Response (iDoR)
Timepoint [8] 0 0
Up to approximately 2 years
Secondary outcome [9] 0 0
All Cohorts: Pharmacokinetic (PK) parameter
Timepoint [9] 0 0
Up to approximately 2 years

Eligibility
Key inclusion criteria
1. Written informed consent
2. =18 years of age (or meets the country's regulatory definition of legal adult age, whichever is greater
3. Pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria:

Cohort A patients:
* Documented EGFR ex20ins mutation status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US).
* Progressed on or after systemic therapy with an agent targeting ex20ins, either alone or in combination with standard platinum-based chemotherapy for the treatment of advanced disease. Patients who discontinued previous treatment due to unacceptable toxicity are eligible.
* Patients with brain metastasis must be neurologically stable. Patients must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period, and they must be on a stable or decreasing dose of corticosteroids and/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Patients with history of uncontrolled seizures or leptomeningeal disease are not eligible.

Cohort B patients:
* Documented EGFR ex20ins mutation status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US).
* Not received prior systemic therapy for locally advanced or metastatic disease. Prior adjuvant/neoadjuvant treatment for early-stage disease must have been completed >6 months prior to the first dose of study treatment.
* Patients with brain metastasis must be neurologically stable. Patients must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period, and they must be on a stable or decreasing dose of corticosteroids and/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Patients with history of uncontrolled seizures or leptomeningeal disease are not eligible.

Cohort C patients:
* Documented EGFR ex20ins mutation status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US).
* Presence of brain metastasis(es), which may be measurable or nonmeasurable by RANO-BM criteria, characterized as one of the following:

* Newly diagnosed and/or progressive brain metastasis (es) not subjected to CNS-directed therapy, OR
* Leptomeningeal disease (LMD) confirmed by a positive cerebrospinal fluid cytology, or unequivocal radiographic and/or clinical determination.

Cohort D patients:
* Documented other non-ex20ins uncommon single or compound EGFRmt status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US). A list of eligible mutations will be provided in a separate manual.
* Patients with brain metastasis must be neurologically stable. Patients must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period, and they must be on a stable or decreasing dose of corticosteroids and/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Patients with history of uncontrolled seizures or leptomeningeal disease are not eligible.
4. Measurable disease per RECIST 1.1.
5. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers (details provided in a laboratory manual). Patients with insufficient tissue may be eligible following discussion with the sponsor.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 17. Adequate organ function, as defined by the hematologic, renal and hepatic laboratory values

4. 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 post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).

5. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose of study drug and for 6 months after the last dose of study treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged to be scientifically or medically incompatible with this study.
2. Has received any of the following within the specific time frame specified:

1. Patient has received Zipalertinib (TAS6417/CLN081) at any time
2. Thoracic radiotherapy =28 days or palliative radiation =14 days prior to the first dose of study treatment
3. Anticancer immunotherapy =28 days prior to the first dose of study treatment
4. Major surgery (excluding placement of vascular access) =28 days prior to the first dose of study treatment.
3. Have any unresolved toxicity of Grade =2 from previous anticancer treatment, except for Grade 2 alopecia or skin pigmentation. Patients with other chronic but stable Grade 2 toxicities may be allowed to enroll after agreement between the investigator and Sponsor.
4. Past medical history of interstitial lung disease, treatment-related pneumonitis (any grade), or evidence of clinically active interstitial lung disease.
5. 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 using Fridericia's formula (QTcF).
6. Is unable to swallow tablets/capsules or has any disease or condition that may significantly affect gastrointestinal absorption of zipalertinib (eg, inflammatory bowel disease, malabsorption syndrome, or prior gastric/bowel resection).
7. 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. Patients with previously treated malignancy if all treatment for that malignancy was completed at least 2 years prior to first dose and no evidence of disease
4. Patients with concurrent malignancy clinically stable and not requiring tumor-directed treatment
8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is not controlled with treatment.
9. History of COVID-19 infection within 4 weeks prior to enrolment and/or has 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 pregnant or lactating.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
20/10/2025
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [2] 0 0
GenesisCare - North Shore - Saint Leonards
Recruitment hospital [3] 0 0
Joondalup Health Campus - Joondalup
Recruitment postcode(s) [1] 0 0
2200 - Bankstown
Recruitment postcode(s) [2] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [3] 0 0
6027 - Joondalup
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Nevada
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Canada
State/province [15] 0 0
Brampton
Country [16] 0 0
France
State/province [16] 0 0
Aslace
Country [17] 0 0
France
State/province [17] 0 0
Basse-Normandie
Country [18] 0 0
France
State/province [18] 0 0
Ile-de-France
Country [19] 0 0
France
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Limousin
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France
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Loire-Atlantique
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France
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Nouvelle-Aquitaine
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France
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Provence Alpes Cote d´Azur
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France
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Rhone-Alpes
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France
State/province [24] 0 0
Val-de-Marne
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France
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Île-de-France
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Germany
State/province [26] 0 0
Baden-Wuerttemberg
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Germany
State/province [27] 0 0
Hamburg (Hansestadt)
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Germany
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Hassen
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Germany
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Hessen
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Germany
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Nordrhein-Westfalen
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Germany
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SAchsen
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Germany
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München
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Germany
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Regensburg
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Hong Kong
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Hong Kong Island
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Italy
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Florence
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Italy
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Forli-Cesena
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Italy
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Ravenna
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Italy
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Torino
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Italy
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Catania
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Italy
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Cremona
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Italy
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Genova
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Italy
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Milan
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Italy
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Modena
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Italy
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Parma
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Italy
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Piacenza
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Italy
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Roma
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Japan
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Aiti
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Japan
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Hukuoka
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Japan
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Miyagi
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Japan
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Osaka
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Japan
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Sizuoka
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Japan
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Tiba
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Japan
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Tokyo
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Japan
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Niigata
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Japan
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Okayama
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Gyeonggi-Do
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Korea, Republic of
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Gyeongsangnamdo [Kyongsangnam-do]
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Korea, Republic of
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Incheon Gwang'yeogsi [Inch'on-Kwangyokshi]
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Korea, Republic of
State/province [60] 0 0
Jeollanam-do
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Korea, Republic of
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Seoul Teugbyeolsi [Seoul-T'ukpyolshi]
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
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Spain
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La Coruña
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Spain
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Malaga
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Spain
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Jaén
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Spain
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Madrid
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Turkey
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Ankara
Country [68] 0 0
Turkey
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Diyarbakir
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Turkey
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Istanbul
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Turkey
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Adana
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Turkey
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Edirne
Country [72] 0 0
United Kingdom
State/province [72] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Taiho Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety and efficacy of zipalertinib in patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations and other mutations.
Trial website
https://clinicaltrials.gov/study/NCT05967689
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Taiho Oncology, INC
Address 0 0
Country 0 0
Phone 0 0
+1 844-878-2446
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05967689