DAY101 Monotherapy or in Combination With Other Therapies for Patients With Solid Tumors

Sponsor
Day One Biopharmaceuticals, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04985604
Collaborator
(none)
168
14
2
53.6
12
0.2

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

Study Type:
Interventional
Anticipated Enrollment :
168 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/2, Open Label Study of DAY101 Monotherapy or Combination With Other Therapies for Patients With Recurrent, Progressive, or Refractory Solid Tumors Harboring MAPK Pathway Aberrations
Actual Study Start Date :
Jul 15, 2021
Anticipated Primary Completion Date :
Jul 31, 2025
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm #1

DAY101 monotherapy

Drug: DAY101
DAY101 tablet for oral use.
Other Names:
  • TAK580, MLN2480
  • Experimental: Arm #2

    DAY101 plus pimasertib

    Drug: DAY101
    DAY101 tablet for oral use.
    Other Names:
  • TAK580, MLN2480
  • Drug: Pimasertib Hydrochloride
    pimasertib capsule for oral use.
    Other Names:
  • pimasertib hydrochloride, AS703026, MSC1936369B
  • Outcome Measures

    Primary Outcome Measures

    1. Phase 1B: Determine the safety of DAY101 in combination with other therapies [Up to 48 months]

      Incidence and severity of adverse events

    2. Phase 1B: Determine the MTD and RP2D of DAY101 in combination with other therapies [Up to 48 months]

      Incidence and severity of adverse events

    3. 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

    1. 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

    2. 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)

    3. 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

    4. 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

    5. 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

    6. 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

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Signed informed consent by patients ≥18 years of age and, assent for patients ≥ 12 up to < 18 years of age

    • 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

    • Patients must have radiographically-recurrent or radiographically-progressive disease that is measurable using the appropriate tumor response criteria (e.g. RECIST version 1.1)

    • Archival tumor tissue (preferably less than 3 years old) or fresh tumor tissue for correlative studies is required

    • If brain metastases are present, they must have been previously treated and be stable as assessed by radiographic imaging

    Exclusion Criteria:
    • Known presence of concurrent activating mutation

    • 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.
    Responsible Party:
    Day One Biopharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT04985604
    Other Study ID Numbers:
    • DAY101-102
    First Posted:
    Aug 2, 2021
    Last Update Posted:
    Jul 29, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 29, 2022