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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04521686




Registration number
NCT04521686
Ethics application status
Date submitted
13/08/2020
Date registered
20/08/2020

Titles & IDs
Public title
Study of LY3410738 Administered to Patients With Advanced Solid Tumors With IDH1 or IDH2 Mutations
Scientific title
A Phase 1 Study of LY3410738 Administered to Patients With Advanced Solid Tumors With IDH1 or IDH2 Mutations
Secondary ID [1] 0 0
2020-002863-77
Secondary ID [2] 0 0
LOXO-IDH-20002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cholangiocarcinoma 0 0
Chondrosarcoma 0 0
Glioma 0 0
Any Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY3410738
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin
Treatment: Drugs - Durvalumab

Experimental: LY3410738 - Phase 1 dose escalation - Multiple doses of LY3410738

Experimental: LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumab - Phase 1 dose expansion - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of LY3410738 alone or in combination with gemcitabine plus cisplatin or in combination with durvalumab


Treatment: Drugs: LY3410738
Oral LY3410738

Treatment: Drugs: Gemcitabine
Intravenous gemcitabine

Treatment: Drugs: Cisplatin
Intravenous cisplatin

Treatment: Drugs: Durvalumab
Intravenous durvalumab
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Objective Response Rate
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [2] 0 0
Assess the safety and tolerability of LY3410738 when administered alone or in combination with cisplatin plus gemcitabine or in combination with durvalumab
Timepoint [2] 0 0
Up to 24 months
Secondary outcome [3] 0 0
To assess the preliminary anti-tumor activity of LY3410738 when administered alone or in combination with cisplatin plus gemcitabine or in combination with durvalumab
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Characterize PK properties of LY3410738 when administered alone or in combination with cisplatin plus gemcitabine or in combination with durvalumab
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [5] 0 0
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma
Timepoint [5] 0 0
Up to 24 months

Eligibility
Key inclusion criteria
1. Evidence of IDH1 R132 mutation (any solid tumor) or circulating tumor DNA IDH2 R140 or IDH2 R172 mutation (cholangiocarcinoma only) as determined by molecular testing performed at a CLIA, ISO/IEC, CAP, or other similarly certified laboratory. For cholangiocarcinoma, chondrosarcoma, and glioma, molecular testing can be performed on tumor tissue or circulating tumor DNA. For all other solid tumor types, molecular testing must be performed on tumor tissue.
2. Availability of an archived tumor tissue sample. Patients without an available archival tumor tissue sample must be discussed with the sponsor's Medical Monitor prior to enrollment.
3. Eastern Cooperative Oncology Group (ECOG) 0-1.
4. At least 18 years of age.
5. Adequate organ function.
6. Ability to swallow capsules or tablets.
7. Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
8. For cholangiocarcinoma patients, must have adequate biliary drainage (per investigator's discretion), with no evidence of ongoing infection.
9. Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment. Patients enrolled to Dose Expansion Cohort 4 shall also follow cisplatin/gemcitabine contraception duration requirements as determined by labels and/or local guidelines. Patients enrolled in dose expansion Cohort 5 should follow durvalumab contraception duration requirements as determined by the durvalumab label and/or local guidelines.

Monotherapy Dose Escalation:
10. A locally advanced or metastatic solid tumor, where standard curative or palliative measures are no longer effective or are not considered appropriate or safe in the opinion of the investigator.
11. Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate by tumor type.
12. Prior IDH1 inhibitor treatment is permitted.

Monotherapy Dose Expansion Cohort 1:
13. Histologically or cytologically confirmed diagnosis of advanced or metastatic cholangiocarcinoma, following 1 to 2 lines of prior systemic treatment for advanced disease. Prior IDH1 inhibitor treatment is not permitted.
14. Measurable disease as determined by RECIST 1.1.

Monotherapy Dose Expansion Cohort 2:
15. A locally advanced or metastatic solid tumor (except for cholangiocarcinoma), where standard curative or palliative measures are no longer effective or are not considered appropriate or safe in the opinion of the investigator.
16. Measurable disease as determined by RECIST 1.1 or RANO as appropriate by tumor types.

Monotherapy Dose Expansion Cohort 3:
17. A locally advanced or metastatic solid tumor, where standard curative or palliative measures are no longer effective or are not considered appropriate or safe in the opinion of the investigator.
18. Non-measurable disease only as determined by RECIST 1.1 or RANO as appropriate by tumor type.

Combination Dose Expansion Cohort 4:
19. Histologically or cytologically confirmed diagnosis of advanced or metastatic cholangiocarcinoma, not eligible for curative resection.
20. No prior systemic therapy for advanced or metastatic disease with the following exceptions:

* Patients who received adjuvant chemotherapy are eligible, if the adjuvant therapy was completed at least 6 months prior to the development of advanced or metastatic disease.
* Patients who are receiving up to two cycles of cisplatin plus gemcitabine as the first line systemic therapy while waiting for results of molecule profiling including IDH1/IDH2 mutational status, are eligible, provided that a radiographic assessment during screening demonstrates the absence of interval disease progression since initiation of chemotherapy treatment, and all other eligibility criteria are met.
21. Measurable disease as determined by RECIST 1.1.

Combination Dose Expansion Cohort 5:
22. Cholangiocarcinoma patients with IDH1 R132, IDH2 R140, or IDH2 R172 mutations
23. Histologically or cytologically confirmed diagnosis of advanced or metastatic cholangiocarcinoma, following 1 or more lines of prior systemic treatment for advanced disease.
24. Measurable disease as determined by RECIST 1.1
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Had an investigational agent or anticancer therapy within 2 weeks; or investigational monoclonal antibody within 4 weeks prior to planned start of LY3410738.
2. Had major surgery within 4 weeks prior to planned start of LY3410738.
3. Had radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment, except for patients receiving whole brain radiotherapy, which must be completed at least 4 weeks prior to the first dose of study treatment.
4. Patients with cholangiocarcinoma: underwent hepatic radiation, chemoembolization and radiofrequency ablation, radioembolization or other locoregional therapy <4 weeks, have history of hepatic encephalopathy of any grade, have ascites requiring intervention such as diuretics or paracentesis, have ongoing cholangitis, have mixed hepatocellular biliary tract cancer histology or history of liver transplant.
5. Have active CNS metastases are not eligible. Patients with asymptomatic and treated brain metastases may participate provided that they are stable and are not requiring steroid treatment. Patients with suspected or confirmed leptomeningeal disease are not eligible even if treated.
6. Have primary CNS tumors are eligible provided that they do not have leptomeningeal disease and are on a stable or decreasing steroid dose for 7 days prior to screening. Patients with evidence of intracranial hemorrhage either by MRI or CT are not eligible
7. Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 at the time of starting study treatment except for alopecia.
8. Have clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of study treatment.
9. Have active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and the sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
10. Known active hepatitis B virus (HBV). Note: Controlled (treated) hepatitis will be allowed if they meet the following criteria, antiviral therapy for HBV must be given for at least 1 month prior to first dose of study drug, and HBV viral load must be less than 2000 IU/ml (104 copies/ml) prior to the first dose of study drug. Those on active HBV therapy with viral loads under 2000 IU/ml (104 copies/ml) should stay on the same therapy throughout the study treatment (Appendix E).
11. Known active hepatitis C virus (HCV). Note: Untreated patients with chronic infection by HCV are allowed on study. In addition, successfully treated patients with chronic infection by HCV (defined as sustained virologic response SVR12 or SVR24) are allowed, as long as a minimum of 4 weeks has elapsed between achieving sustained viral response (SVR12 or SVR24) and starting study drug.
12. Known human immunodeficiency virus (HIV); excluded due to potential drug-drug interactions between anti-retroviral medications and LY3410738.
13. Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (Appendix F) and/or P-gp inhibitors (Appendix G).
14. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
15. Active second malignancy unless in remission and with life expectancy > 2 years. Refer to protocol exclusion criteria (Section 4.2) for examples of allowed second malignancies.
16. Pregnancy, lactation or plans to breastfeed during the study or within 3 months of the last dose of study intervention.
17. Patients with known hypersensitivity to any component of LY3410738 or its formulation.

Combination Dose Expansion Cohort 5:
18. Prior treatment with anti-PD 1 or anti-PD L1 therapies.
19. History of Grade 3 or higher immune-related adverse events (irAEs).
20. Active autoimmune disease that has required systemic anti-autoimmune treatment in the past 2 years.

Endocrine replacement therapy is not considered a form of systemic therapy and is allowed.
21. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids which should not exceed 10 mg/day of prednisone or equivalent corticosteroid.
22. Active interstitial lung disease or history of noninfectious pneumonitis Grade 2 or higher that required treatment with systemic corticosteroids or immunosuppressive drugs.
23. History of hypersensitivity to durvalumab or any excipient.
24. Has received a live vaccine within 30 days prior to the first dose of study drug.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2025
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
France
State/province [13] 0 0
Bordeaux
Country [14] 0 0
France
State/province [14] 0 0
Villejuif Cedex
Country [15] 0 0
Hong Kong
State/province [15] 0 0
Shatin, New Territories
Country [16] 0 0
Japan
State/province [16] 0 0
Chiba
Country [17] 0 0
Japan
State/province [17] 0 0
Kanagawa
Country [18] 0 0
Japan
State/province [18] 0 0
Osaka
Country [19] 0 0
Japan
State/province [19] 0 0
Shizuoka
Country [20] 0 0
Japan
State/province [20] 0 0
Tokyo
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul-teukbyeolsi [Seoul]
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Singapore
State/province [23] 0 0
Singapore
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid
Country [26] 0 0
Taiwan
State/province [26] 0 0
Taichung City
Country [27] 0 0
Taiwan
State/province [27] 0 0
Tainan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Loxo Oncology, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Hui Liu
Address 0 0
Medical Monitor
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04521686