Study of HBI-8000 With Nivolumab in Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer

Phase 1

Completed

• Conditions: Melanoma; Renal Cell Carcinoma; Non-Small Cell Lung Cancer
• Interventions: Drug: HBI-8000 in combination with nivolumab

• Registration Number: NCT02718066
• Lead Sponsor: HUYABIO International, LLC.

Brief Summary

A Phase 1b/2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination with Nivolumab in Patients with Advanced Solid Tumors Including Melanoma, Renal Cell Carcinoma (RCC), and Non-Small Cell Lung Cancer (NSCLC).

The primary objective of this study is:

-To evaluate the safety and tolerability of HBI-8000 when combined with a standard dose and regimen of nivolumab, and to evaluate frequency and severity of toxicities of this combination treatment

The secondary objectives of this study include:

* To explore the efficacy of study treatment as measured by Objective Response Rate (ORR), Disease Control Rate (DCR), Clinical Benefit Rate (CBR), Duration of Response (DoR), Progression-Free Survival (PFS) in all subjects treated at RP2D

* To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with nivolumab administered once every two weeks (Phase 1b all sites)

* To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with nivolumab administered per package insert dose and administration (Phase 2 selected sites)

* To characterize the effect of HBI-8000 on the electrocardiogram QT corrected (QTc) interval (Phase 1b only)

Exploratory:

* To investigate the kinetics and extent of histone acetylation in peripheral blood mononuclear cells (PBMC) at the RP2D of HBI-8000 (Phase 2 only)

* To explore potential biomarkers for disease response through sequential sampling of blood and/or tumor tissue in subjects consenting to correlative sub-studies at participating sites (Phase 2 only)

Dose Escalation (Phase 1b) will include up to 18 subjects, followed by Cohort Expansion (Phase 2) including up to 100 subjects (melanoma up to 60 subjects and NSCLC up to 40 subjects at MTD and/or RP2D.

Detailed Description

A Phase 1b/2 Study to Assess the Safety and Efficacy of HBI-8000 in Combination with Nivolumab in Patients with Advanced Solid Tumors Including Melanoma, Renal Cell Carcinoma (RCC), and Non-Small Cell Lung Cancer (NSCLC).

The primary objective of this study is:

-To evaluate the safety and tolerability of HBI-8000 when combined with a standard dose and regimen of nivolumab, to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) and to evaluate frequency and severity of toxicities of this combination treatment

The secondary objectives of this study include:

* To explore the efficacy of study treatment as measured by Objective Response Rate (ORR), Disease Control Rate (DCR), Clinical Benefit Rate (CBR), Duration of Response (DoR), Progression-Free Survival (PFS) in all subjects treated at RP2D

* To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination with nivolumab administered once every two weeks (Phase 1b all sites; Phase 2 selected sites)

* To characterize the effect of HBI-8000 on the electrocardiogram QT corrected (QTc) interval (Phase 1b only)

Exploratory:

-To investigate the kinetics and extent of histone acetylation in peripheral blood mononuclear cells (PBMC) at the RP2D of HBI-8000 (Phase 2 only)

Dose Escalation (Phase 1b) will include up to 18 subjects, followed by Cohort Expansion (Phase 2) including up to 100 subjects (melanoma up to 60 subjects and NSCLC up to 40 subjects) at MTD and/or RP2D.

HBI-8000 tablets will be administered at 20, 30, 40 mg/dose, orally twice a week until MTD or 40 mg in Phase 2, if MTD is not reached.

Nivolumab: 240 mg intravenous infusions every 2 weeks for Phase 1b and in accordance with the manufacturer package insert and institution's prescribing practice for Phase 2.

A treatment cycle consists of 28 days. Treatment continues until disease progression or unacceptable toxicity.

Study Timeline

• Study First Submitted: 2016-03-15
• Study First Submitted QC: 2016-03-23
• Study First Posted: 2016-03-24
• Study Start: 2016-08
• Primary Completion: 2023-09
• Study Completion: 2023-09
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-08
• Last Update Posted: 2023-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HBI-8000 in combination with nivolumab	HBI-8000 in combination with nivolumab	HBI-8000 dose escalation 20mg, 30mg, 40mg, orally, twice weekly; in combination with Nivolumab 240mg intravenous infusions every 2 weeks for Phase 1b and in accordance with the manufacturer package insert and institution's prescribing practice for Phase 2.

Primary Outcome Measures

Name	Time	Method
Determination of the Recommended for Phase 2 Dose (RP2D) (mg)	12 months	Determination of the Recommended for Phase 2 Dose (RP2D) (mg)

Secondary Outcome Measures

Name	Time	Method
Efficacy Outcome: Response Rate (%).	18 months	Objective Response Rate (ORR)

Trial Locations

Locations (6)

[Site 02] Mayo Clinic Arizona; 🇺🇸 Phoenix, Arizona, United States

[Site 01] Hematology - Oncology Associates of the Treasure Coast; 🇺🇸 Port Saint Lucie, Florida, United States

[Site 11] University of California, San Diego Medical Center; 🇺🇸 La Jolla, California, United States

[Site 09] H. Lee Moffitt Cancer Center and Research Institute, Inc.; 🇺🇸 Tampa, Florida, United States

[Site 12] University of Texas M.D. Anderson Cancer Center - Investigational Cancer Therapeutics; 🇺🇸 Houston, Texas, United States

[Site 13] Frederick Memorial Hospital d/b/a James M Stockman Cancer Institute; 🇺🇸 Frederick, Maryland, United States