DAY101 Monotherapy or in Combination With Other Therapies for Patients With Solid Tumors
Study Details
Study Description
Brief Summary
This is a Phase 1b/2, multi-center, open label umbrella study of patients ≥12 years of age with recurrent or progressive solid tumors with alterations in the key proteins of the RAS/RAF/MEK/ERK pathway, referred to as the MAPK pathway..
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Study DAY101-102 (master study) and sub-studies will consist of a screening period, a treatment period, a safety follow-up period, and a long-term follow-up period where survival, status and subsequent anticancer therapies are collected.
DAY101 will be evaluated alone or combined with a different targeted therapy in each sub-study. The Phase1b part of each sub-study will evaluate the safety of the combination and select the dose for the Phase 2 part. The Phase 2 part of each sub-study will evaluate anti-tumor activity.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm #1 DAY101 monotherapy |
Drug: DAY101
DAY101 tablet for oral use.
Other Names:
|
Experimental: Arm #2 DAY101 plus pimasertib |
Drug: DAY101
DAY101 tablet for oral use.
Other Names:
Drug: Pimasertib Hydrochloride
pimasertib capsule for oral use.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase 1B: Determine the safety of DAY101 in combination with other therapies [Up to 48 months]
Incidence and severity of adverse events
- Phase 1B: Determine the MTD and RP2D of DAY101 in combination with other therapies [Up to 48 months]
Incidence and severity of adverse events
- Phase 2: Evaluate the efficacy of DAY101 monotherapy [Up to 48 months]
Overall response rate (ORR) as assessed by the proportion of patients with the best overall confirmed response of complete response (CR) or PR according to RECIST ver 1.1
Secondary Outcome Measures
- Phase 1b: Assess efficacy of DAY101 in combination with other therapies [Up to 48 months]
Duration of response (DOR) in patients with best overall response of CR or PR
- Phase 1b & 2: Assess additional efficacy parameters of DAY101 alone and in combination with other therapies [Up to 48 months]
Duration of progression-free survival (PFS) and overall survival (OS)
- Phase 1b & 2: Characterize tumor responses observed with DAY101 alone and in combination with other therapies [Up to 48 months]
Time to response (TTR) in patients with best overall response of CR or PR; and comparing the DOR in patients with CR or PR with the DOR observed with the immediate prior line of anticancer treatment
- Phase 1b & 2: Characterize the pharmacokinetic (PK) profile of DAY101 alone and in combination with other therapies [Up to 48 months]
Measure plasma concentration of DAY101
- Phase 1b & 2: Characterize the pharmacodynamic (PD) profile of DAY101 alone and in combination with other therapies [Up to 48 months]
Evaluate changes from baseline of phosphorylated ERK and other relevant biomarkers
- Phase 2: Assess the safety and tolerability of DAY101 as monotherapy, or in combination with other therapies [Up to 48 months]
Incidence and severity of adverse events
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed informed consent by patients ≥18 years of age and, assent for patients ≥ 12 up to < 18 years of age
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Patients must have a histologically confirmed diagnosis of tumor with concurrent MAPK pathway alteration as assessed by sequencing, PCR, FISH, or another clinically accepted molecular diagnostic method recognized by local laboratory or regulatory agency
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Patients must have radiographically-recurrent or radiographically-progressive disease that is measurable using the appropriate tumor response criteria (e.g. RECIST version 1.1)
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Archival tumor tissue (preferably less than 3 years old) or fresh tumor tissue for correlative studies is required
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If brain metastases are present, they must have been previously treated and be stable as assessed by radiographic imaging
Exclusion Criteria:
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Known presence of concurrent activating mutation
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Patients with current evidence or a history of central serous retinopathy (CSR), retinal vein occlusion (RVO)
Substudy A-specific exclusion criterion:
- Prior therapy with BRAF-, MEK-, or MAPK-directed inhibitor therapy, except for tumor types and indications where such therapy has been approved by the FDA or applicable regulatory authorities
Substudy B-specific exclusion criterion:
- Prior receipt of any pan-RAF inhibitor therapy (e.g., LXH254/naporafenib, BGB- 283, BGB-3245, belvarafenib)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | The Angeles Clinic | Los Angeles | California | United States | 90025 |
2 | Hoag Health | Newport Beach | California | United States | 92663 |
3 | University of Colorado Hospital | Aurora | Colorado | United States | 80045 |
4 | Cancer Specialists of North Florida | Jacksonville | Florida | United States | 32256 |
5 | University of Miami Sylvester Comprehensive Cancer Center | Miami | Florida | United States | 33136 |
6 | Community North Cancer Center | Indianapolis | Indiana | United States | 46250 |
7 | OHSU Knight Cancer Institute | Portland | Oregon | United States | 97239 |
8 | UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15213 |
9 | Vanderbilt-Ingram Cancer Center Recruitment and Eligibility Office | Nashville | Tennessee | United States | 37232 |
10 | Dong-A University Hospital | Busan | Korea, Republic of | ||
11 | Asan Medical Center | Seoul | Korea, Republic of | ||
12 | Samsung Medical Center | Seoul | Korea, Republic of | ||
13 | Severance Hospital, Yonsei University Health System | Seoul | Korea, Republic of | ||
14 | Hospital Universitario Ramón y Cajal | Madrid | Spain |
Sponsors and Collaborators
- Day One Biopharmaceuticals, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DAY101-102