A study in patients with skin cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Huyabio International LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Apr 2022 → ongoing

Decision date (initial)

2024-10-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

HUYABIO International, LLC

External identifiers

EU CT number

2024-516914-39-00

EudraCT number

2019-002521-30

ClinicalTrials.gov

NCT04674683

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare, between Test (HBI-8000 + nivolumab) and Control (placebo
+ nivolumab) arms:
• Progression-free Survival (PFS), defined as the time (in days) from the date of randomization to the first date of documented disease progression according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as determined by BIRC, or the date of death due to any cause, whichever occurs first.

Secondary objectives 3

1. To compare, between Test and Control arms: Objective Response Rate (ORR), defined as the percentage of patients enrolled in each study arm with best response of confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the Blinded Independent Review Committee (BIRC).
2. To compare, between Test and Control arms: Overall Survival (OS) defined as the time from the date of randomization to the date of death due to any cause.
3. To compare, between Test and Control arms: Safety defined as the incidence rate of adverse events. The NCI-CTCAE v5.0, will serve as the reference document for choosing the appropriate terminology to grade the severity of AEs, and to assess the causal relationship, and outcomes at the time of screening through to the completion of the end of treatment safety follow up visits.

Conditions and MedDRA coding

Metastatic or unresectable melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Histopathologically confirmed diagnosis of non-uveal, Stage III (unresectable), or Stage IV (metastatic) melanoma according to AJCC staging system (8th edition).
2. Known BRAF V600 mutation status or consent to BRAF V600 mutation testing before randomization.
3. Tumor tissue available for PD-L1 testing at central Laboratory or local laboratory; results must be obtained prior to randomization. In the event when archived tumor tissue is not available, new tumor biopsy or historical PD-L1 test results may be used for randomization, however tumor tissue, either taken previously or newly acquired, must be provided for central biomarker confirmation for final data analyses. PD-L1 expression level is required for randomization. In order to be randomized, a patient must be classified as PD-L1 positive or PD-L1 negative according to the following criteria: • PD-L1 positive (≥1% tumor cell membrane staining in a minimum of a hundred evaluable tumor cells) vs • PD-L1 negative (< 1% tumor cell membrane staining in a minimum of a hundred evaluable tumor cells) Note: If an insufficient amount of tumor tissue is available prior to the start of the Screening phase, patients must consent to allow the acquisition of additional tumor tissue for performance of biomarker analyses.
4. Males or females 12 years of age or older
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 for age ≥18 years, Lansky performance status ≥80% for age 12-17 years.
6. At least one measurable lesion defined by RECIST 1.1 criteria separate from the lesion to be used for tumor tissue collection for PDL1 testing, not counting brain metastasis with: • Longest diameter ≥10 mm by computed tomography (CT) (when slice thickness is ≤5 mm); or ≥ 2 × slice thickness (when slice thickness is >5 mm) • Pathologically enlarged lymph node: ≥15 mm in short axis by CT (when slice thickness is ≤5 mm) • Clinical: ≥10 mm (that can be accurately measured with calipers) (refer to Appendix 5)
7. Have not received anti-PD-1, anti-PD-L1 or other systemic therapy for unresectable or metastatic melanoma, except for the following, provided that the patient recovered from all treatment related toxicities: a. BRAF mutation targeted therapy >4 weeks before administration of Study Treatment. b. Adjuvant or neoadjuvant therapy with PD-1 or PD-L1 inhibitors, anti- cytotoxic T lymphocyte-associated protein 4 (CTLA4) is allowed if disease progression/or recurrence had occurred at least 6 months after the last dose of neoadjuvant/adjuvant therapy and prior to receiving the first dose on this study and no clinically significant immune related toxicities leading to treatment discontinuation were observed. c. Adjuvant interferon therapy must have been completed >6 weeks before administration of Study Treatment
8. Any prior radiotherapy or minor surgery must be completed at least 2 weeks and 1 week respectively before Day 1 dosing and recovered from all treatment related toxicities.
9. Screening laboratory results within 14 days prior to randomization: a. Hematology: white blood cells (WBC) ≥3000/μL, neutrophils ≥1500/μL, platelets ≥100 × 103/μL, hemoglobin ≥10.0 g/dL independent of transfusion. The use of erythropoietic growth factor to achieve Hgb ≥10 g/dl is acceptable. b. CrCL ≥30 mL/min using Cockcroft-Gault formula Appendix 3 [Cockcroft and Gault, 1976]. c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN), alkaline phosphatase ≤2.5 × ULN unless bone metastases present (patients with documented bone metastases: alkaline phosphatase <5 × ULN), bilirubin ≤1.5 × ULN (unless known Gilbert’s disease where it must be ≤3 × ULN), serum albumin ≥3.0 g/dL.
10. Negative serum pregnancy test at baseline for women of childbearing potential (WOCBP).
11. Females of childbearing potential (non-surgically sterile or premenopausal female capable of becoming pregnant) and all males (due to potential risk of drug exposure through the ejaculate) must agree to use an adequate method of contraception including a highly effective method and a barrier method during the study and for 5 months after the last dose of Study Drug. Highly effective contraception used by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Refer to Section 8.3 for details and definitions of WOCBP, postmenopausal females, and contraception guidance
12. Have the ability to understand and the willingness to sign a written informed consent document, comply with study scheduled treatment, visits and assessments.

Exclusion criteria 25

1. History of ≥ Grade 3 hypersensitivity reactions to monoclonal antibodies.
2. Previous treatment with a PD-1, PD-L1, PD-L2, CTLA-4 inhibitor, or any other agents targeting T-cell co-stimulation or immune checkpoint pathways for unresectable or metastatic melanoma.
3. Recipient of solid organ transplant.
4. History of a cardiovascular illness including: congestive heart failure (New York Heart Association Grade III or IV); unstable angina or myocardial infarction within the previous 6 months; or symptomatic cardiac arrhythmia despite medical management. QT interval corrected by heart rate using Fridericia’s correction formula (QTcF) >450 ms in male or >470 ms in female, or congenital long QT syndrome.
5. Uncontrolled hypertension, systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >100 mmHg.
6. Patients with new, active, or progressive brain metastases or leptomeningeal disease, except when considered for a separate open label cohort for special population
7. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer, or bowel resection that affects absorption of orally administered drugs.
8. Active, known, or suspected autoimmune disease, except for Type I diabetes mellitus, hypothyroidism requiring only hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic therapy.
9. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
10. Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS).
11. Hepatitis B surface antigen positive or hepatitis C antibody positive. Further investigation per institutional practices may be performed to exclude active infection.
12. Patients with a condition requiring chronic systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days before administration of Study Treatment. Inhaled or topical steroids, or adrenal replacement dose of corticosteroids at dose ≤10 mg/day prednisone (or equivalent) are permitted.
13. Use of other investigational agent (drug or vaccine not marketed for any indication) within 28 days before administration of Study Treatment. If the investigational agent is a monoclonal antibody, then use within 3 months, before administration of Study Treatment
14. Pregnant or breast-feeding women.
15. Have a history of any other malignancy unless in remission for 2 years, or locally curable cancers that have been treated with curative intent with no evidence of recurrence, such as: • Basal or squamous cell skin cancer • Superficial bladder cancer • Carcinoma in situ of cervix or breast • Incidental prostate cancer • Non-melanomatous skin cancer • Prostate cancer treated with curative intent with serum prostate-specific antigen (PSA) <2.0 ng/mL
16. Patients with medical conditions requiring administration of strong cytochrome P450 (CYP) 3A4 Inducers and Inhibitors with no alternative therapy.
17. Uncontrolled adrenal insufficiency or active chronic liver disease.
18. Has received approved live vaccine/ live attenuated vaccines within 30 days of planned Cycle 1 Day 1. Inactivated viral vaccines or vaccines based on subviral component are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are not allowed. Coronavirus disease 2019 COVID-19 vaccination should be administered at least 7 days before Cycle 1 Day 1.
19. Underlying medical conditions that, in the Investigator’s opinion, will make the administration of Study Treatment hazardous or obscure the interpretation of toxicity determination or adverse events.
20. Patients with a history of or active interstitial lung disease (ILD) or non-infectious pneumonitis.
21. Patient with prior organ or hematopoietic cell transplant (HCT), including allogeneic HCT.
22. Patients with known sensitivity to any of the ingredients of the Study Treatment.
23. Patients who received radiation therapy within 14 days of the first dose of the Study Treatment.
24. Patients who take drugs that prolong the QT interval or cause torsades de pointes or produce significant ventricular dysrhythmias.
25. Patients that are unwilling or unable to comply with the procedures required in this protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is Progression Free Survival PFS. (PFS) is defined as the time (in days) from the date of randomization to the first date of documented progression as determined by the BIRC, or the date of death due to any cause, whichever occurs first.

Secondary endpoints 2

1. Objective Response Rate (ORR) The ORR is defined as the percentage of patients enrolled in each arm with a best response of confirmed CR or PR as determined by the BIRC
2. Overall Survival (OS) The OS is defined as the time from randomization date to the date of death due to any cause.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Huyabio International LLC

Sponsor organisation

Huyabio International LLC

Address

12531 High Bluff Drive Suite 138

City

San Diego

Postcode

92130-3588

Country

United States

Scientific contact point

Organisation

Huyabio International LLC

Contact name

Clinical trial Information

Public contact point

Organisation

Huyabio International LLC

Contact name

Clinical trial Information

Third parties 4

Locations

6 EU/EEA countries · 54 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 33 files

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

Application history

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