Phase I Study of HL-085 in Patients With Advanced Solid Tumors

NCT03976050 | Terminated Phase 1 FDA Drug

• 1 other identifier: HL-085-US-101
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

The study drug, HL-085 is a MEK inhibitor with the potential indication for cancers. It is an oral medication to be given daily. The purposes of this study is to find answers to the following research questions:

1. 1.What is the highest tolerable dose of HL-085 that can be given to subjects when given orally (by mouth) on a twice daily basis?
2. 2.What are the side effects of HL-085?
3. 3.How much HL-085 is in the blood at specific times after dosing and how does the body get rid of the HL-085?

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (3)

• Adverse events (AEs)

  An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

  Duration of the study, estimated to be approximately 24 months.

• Dose limitation toxicities (DLT)

  A DLT is defined as the occurrence of any of the following AE considered possibly, probably, or definitely related to the IP, HL-085, by the Investigator and/or the Sponsor that occurs during Cycle 1 as described in below: * Any death not clearly due to the underlying disease or extraneous causes; or * Non-hematologic toxicities Grade 3 or higher. * Grade 3 thrombocytopenia with clinically significant bleeding, or other hematologic toxicity at Grade 4 or above. * Neutropenic fever * liver parameter abnormalities * Any toxicity requiring permanent discontinuation of the IP

  During Cycle 1 (the first 28 days)

• Maximum tolerated dose (MTD)

  MTD is defined as the highest dose level at which DLT occurs in less than 33.3% of subjects.

  MTD will be determined when DLT occurs in great or equal to 33.3% of the same cohort subjects during During Cycle 1 (the first 28 days)

Secondary Outcomes (2)

• cMAX

  Duration of the study, estimated to be approximately 24 months

• Overall response rate (ORR)

  Duration of the study, estimated to be approximately 24 months

Other Outcomes (1)

• pERK expression

  Duration of the study, estimated to be approximately 24 months

Study Arms (1)

Dose escalation

EXPERIMENTAL

Subjects in the dose escalation cohorts will receive ascending doses of HL-085 until the MTD is determined. The first three subjects will receive twice-daily doses (BID) of HL-085 6 mg. Additional cohorts may receive doses of HL-085 9, 12 or 18 mg BID respectively and sequentially. If DLTs are observed in \<33.3% of subjects at the 18 mg dose.

Drug: HL-085

Interventions

HL-085 DRUG

HL-085 is a MEK inhibitor with potential indication for cancers. it will be given twice daily continuously in the study until disease progression; or the risks outweigh the benefits, if the subject continues study treatment; or subjects with poor compliance; or subjects need to receive or have already started alternative anti-tumor drugs; or Subjects who need to receive or have already started alternative any other concomitant medication and/or treatment, which would significantly impact their safety; or interruption of IP administration for more than 14 days due to IP-related AEs.

Also known as: No other interventions

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a pathologically documented solid tumor(s) that has relapsed from, or is refractory to standard treatment, or for which no standard treatment is available.
• Must have at least one measurable lesion as defined by RECISTv1.1 criteria for solid tumors.
• Must have received biological chemotherapy, immunotherapy or radiotherapy ≥4 weeks prior to starting the study treatment. Must have received small molecule chemotherapy ≥2 weeks or five half-lives (whichever is longer) prior to starting the study treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy ≥3 months (as judged by the Investigator).
• Must have adequate hematologic, hepatic and renal function.

You may not qualify if:

• Have undergone or plan to have major surgery or experienced severe trauma ≤28 days prior to starting the study treatment.
• Known hypersensitivity to IP ingredients or their analogues.
• Prior therapy with a MEK-inhibitor
• Receipt of any other investigational agent therapy within 4 weeks prior to starting study treatment.
• Any concurrent therapy for cancer treatment.
• Have active central nervous system lesion.
• Receiving and unable to discontinue medication which are strong inducers, strong inhibitors or enzyme substrates of cytochrome P450 CYP2C9 and CYP2C19 from 14 days prior to treatment.
• Grade 3 bleeding symptoms (NCI-CTCAE v5.0) within 4 weeks prior to starting study treatment.
• Unable to swallow IP or has refractory nausea and vomiting, malabsorption, external biliary diversion, or any significant small bowel resection that may interfere with adequate absorption of IP.
• ECG QTcB≥480msec in screening, or history of congenital long QT syndrome.
• Left ventricular ejection fraction (LVEF) \<50%.
• History major cerebrovascular diseases within 6 months prior to enrollment.
• Infectious diseases requiring systemic treatment.
• History or current evidence of retinal diseases.
• Have active/chronic infection with hepatitis C, or positive hepatitis B surface antigen (HBsAg), or active/chronic infection with human immunodeficiency virus (HIV).

Sponsors & Collaborators

• Shanghai Kechow Pharma, Inc.: lead

Study Sites (2)

Livestrong Cancer Institute, Dell Medical School, The University of Texas at Austin

Austin, Texas, 78712, United States

Location

Next Oncology

San Antonio, Texas, 78229, United States

Location

Study Officials

• Yi Liu, MD, PhD

  KeChow Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2019
• First Posted: June 5, 2019
• Study Start: June 17, 2019
• Primary Completion: November 12, 2020
• Study Completion: November 12, 2020
• Last Updated: November 18, 2020

Record last verified: 2020-11

Locations

US (2)