A Phase 2 Study to Test Effects of Using DAY101 in Children with Brain Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Day One Biopharmaceuticals Inc., Day One Biopharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Sep 2021 → ongoing

Decision date (initial)

2024-07-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Day One Biopharmaceuticals, Inc. (Day One)

External identifiers

EU CT number

2024-510691-20-00

EudraCT number

2020-003657-30

ClinicalTrials.gov

NCT04775485

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Safety, Efficacy

Arm 1 (Low-Grade Glioma)
To evaluate the efficacy of tovorafenib as measured by the overall response rate (ORR) as determined by an independent radiology review committee (IRC) following treatment with tovorafenib in pediatric patients aged 6 months to 25 years, inclusive, with a relapsed or progressive low-grade glioma harboring a known activating BRAF alteration

Arm 2 (Low-Grade Glioma Extension)
To assess the safety and tolerability of tovorafenib in pediatric patients aged 6 months to 25 years, inclusive, with a relapsed or progressive low-grade glioma harboring a known or expected to be activating RAF alteration

Arm 3 (Advanced Solid Tumor)
To evaluate the preliminary efficacy of tovorafenib as measured by the overall response rate (ORR) as determined by the treating investigator following treatment with tovorafenib in pediatric patients aged 6 months to 25 years, inclusive, with a relapsed or progressive advanced solid tumor harboring a known or expected to be activating RAF fusion

Secondary objectives 3

1. Arm 1 (Low-Grade Glioma): To assess safety and tolerability of tovorafenib; To determine the relationship between pharmacokinetics (PK) and drug effects, including efficacy and safety
2. Arm 2 (Low-Grade Glioma Extension): To determine the ORR based on RANO-HGG criteria as determined by the treating investigator
3. Arm 3 (Advanced Solid Tumor): To assess the safety and tolerability of tovorafenib in pediatric patients with advanced solid tumors

Conditions and MedDRA coding

RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors in pediatric patients

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Spanish Agency For Medicines And Health Products

EMA paediatric investigation plan (PIP)

EMEA-002763-PIP01-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients must be age 6 months to 25 years, inclusive, with: a) Arm 1 (Low-Grade Glioma): A relapsed or progressive low-grade glioma (LGG) with a documented known activating BRAF alteration. b) Arm 2 (Low-Grade Glioma Extension): A relapsed or progressive low-grade glioma with a documented known or expected to be activating BRAF mutation or RAF fusion. c) Arm 3 (Advanced Solid Tumor): Locally advanced or metastatic solid tumor with a documented known or expected to be activating RAF fusion.
2. Patients must have histopathologic verification of malignancy at either original diagnosis or relapse.
3. Must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression (Arm 1 and Arm 2).
4. Patients must have evaluable and/or measurable disease as specified below: a) Arm 1 (Low-Grade Glioma):Must have at least one measurable lesion. b) Arm 2 (Low-Grade Glioma Extension): Must have evaluable and/or measurable disease c) Arm 3 (Advanced Solid Tumor): Must have at least one measurable lesion
5. Patients must have Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.

Exclusion criteria 5

1. Patient has symptoms of clinical progression without radiographically recurrent or radiographically progressive disease.
2. Patient has history of any major disease, other than the primary malignancy under study, that might interfere with safe protocol participation
3. Patient has major surgery within 14 days (2 weeks) prior to C1D1
4. Patient has clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to C1D1
5. Patient is currently enrolled in any other investigational treatment study. Participation in a concurrent observational or bio-sampling study is allowed.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Arm 1 (Low-Grade Glioma): ORR by RANO-HGG criteria; Arm 2 (Low-Grade Glioma Extension): Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities; Arm 3 (Advanced Solid Tumor): Measured by the proportion of patients with best overall confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 or RANO-HGG criteria

Secondary endpoints 3

1. Arm 1 (Low-Grade Glioma): Type, frequency, and severity of AEs and laboratory abnormalities; -Pharmacokinetic profile of DAY101 (e.g., area under the concentration-time curve [AUC], Cmin, etc.); Time following initiation of DAY101 to progression or death in patients treated with DAY101 - length of response in patients with best overall confirmed response of CR or PR; Time to first response following initiation of DAY101 in patients with best overall confirmed response of CR or PR
2. Arm 2 (Low-Grade Glioma Extension): -Measured by the proportion of patients with best overall confirmed response of CR or PR as determined by the RANO criteria; Measured by the proportion of patients with best overall confirmed response of CR or PR by RAPNO–low-grade glioma criteria
3. Arm 3 (Advanced Solid Tumor): Type, frequency, and severity of AEs and laboratory abnormalities; Pharmacokinetic profile of DAY101 (e.g., AUC, Cmin, etc.)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Day One Biopharmaceuticals Inc.

Sponsor organisation

Day One Biopharmaceuticals Inc.

Address

2000 Sierra Point Parkway Suite 501

City

Brisbane

Postcode

94005-1874

Country

United States

Scientific contact point

Organisation

Day One Biopharmaceuticals Inc.

Contact name

FIREFLY Clinical Trial Team

Public contact point

Organisation

Day One Biopharmaceuticals Inc.

Contact name

FIREFLY Clinical Trial Team

Third parties 25

Day One Biopharmaceuticals Inc.

Sponsor organisation

Day One Biopharmaceuticals Inc.

Address

1800 Sierra Point Parkway Suite 200

City

Brisbane

Postcode

94005-1812

Country

United States

Scientific contact point

Organisation

Day One Biopharmaceuticals Inc.

Contact name

FIREFLY Clinical Trial Team

Public contact point

Organisation

Day One Biopharmaceuticals Inc.

Contact name

FIREFLY Clinical Trial Team

Third parties 25

Sponsor responsibilities

Article 77 compliance

Day One Biopharmaceuticals Inc.

Contact point sponsor

Day One Biopharmaceuticals Inc.

Article 77 implementation

Day One Biopharmaceuticals Inc.

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 115 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications