A Phase 1b Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic NSCLC

NCT02346370 | Terminated Phase 1 Results

• 1 other identifier: HALO-107-201
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 8

Brief Summary

A Phase 1b study for participants with Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) to participate in 1 of 2 portions of this study. The first portion is Dose Escalation in which participants are tested with PEGPH20 at various doses (1.6, 3.0, 2.2 and 2.8 micrograms/kilogram (ug/kg)) in addition to dosing with the standard dose of docetaxel (PDoc) of 75 milligrams/meter squared (mg/m\^2) once every 21-day cycle. Based on observations on the safety and tolerability of study treatment from dose escalation cohorts dosed to date (1.6 and 3.0 ug/kg of PEGPH20), two additional dose levels will be tested, 2.2 and 2.8 ug/kg. Up to 30 additional participants may be enrolled to test these dose levels. The second portion of Phase 1b is Cohort Expansion in which the recommended Phase 2 dose (RP2D) of PDoc identified in dose escalation is administered every 21 days to approximately 50 participants with high hyaluronan (HA-high) prospectively measured in their tumor tissue.

Conditions

Non-small Cell Lung Cancer

Keywords

Recurrent, previously treated, locally advanced or metastatic NSCLC (non small cell lung cancer)

Outcome Measures

Primary Outcomes (3)

• Number of Dose Limiting Toxicities (DLTs)

  DLTs were defined as adverse events (AEs) that occurred during Cycle 1 in the Dose Escalation portion of the study, and deemed by the Investigator as related to study treatment.

  Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)

• Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel

  Throughout the Treatment Period, the assessment of safety was based on AEs, including deaths, non-serious AEs, and serious adverse events, AEs leading to discontinuation of study treatment, and results of vital sign measurements and clinical laboratory assessments (including hematology, clinical chemistry, coagulation parameters, and urinalysis). Additionally, thromboembolic (TE) events were deemed by the Sponsor as AEs of special interest. AEs and laboratory values were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

  From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months

• Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of PEGPH20

  Cycle 1 of Dose Escalation portion (Cycle 1 = 21 days)

Secondary Outcomes (11)

• Phase 1b: Maximum Plasma Concentration (Cmax) of PEGPH20 and Docetaxel

  PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

• Phase 1b: Minimum Plasma Concentration (Cmin) of PEGPH20 and Docetaxel

  PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

• Phase 1b: Time to Maximum Plasma Concentration (Tmax) of PEGPH20 and Docetaxel

  PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

• Phase 1b: Terminal Half-life (t1/2) of PEGPH20 and Docetaxel

  PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

• Phase 1b: Area Under the Plasma Concentration-Time Curve for PEGPH20 and Docetaxel

  PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2

Study Arms (1)

PEGPH20 + Docetaxel

EXPERIMENTAL

PEGylated recombinant human hyaluronidase PH20 (PEGPH20) (1.6, 3.0, or 2.2 micrograms per kilogram (ug/kg)) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an intravenous (IV)-infusion over 10 minutes, approximately 1 milliliter/minute (mL/min) (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 milligrams/meter squared (mg/m\^2)) was administered on Day 2 of each 21-day cycle.

Drug: PEGylated recombinant human hyaluronidase PH20; Drug: Docetaxel

Interventions

PEGylated recombinant human hyaluronidase PH20 DRUG

Also known as: PEGPH20

PEGPH20 + Docetaxel

Docetaxel DRUG

Also known as: Taxotere

PEGPH20 + Docetaxel

Eligibility Criteria

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

You may qualify if:

• Signed, approved Informed Consent.
• Histologically confirmed and documented previously treated Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC), having failed 1 previous platinum chemo regimen for locally advanced or metastatic disease.
• Cohort Expansion: Available archival tumor tissue block or 5-10 unstained, consecutive core biopsy slides from one archival tumor block that meet specific tissue requirements.
• Cohort Expansion: One or more tumors measurable on computed tomography/magnetic resonance imaging (CT/MRI) scan per Response Evaluation Criteria on Solid Tumors (RECIST) v 1.1 (Eisenhauer 2009; Appendix C).
• Participants may have failed a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) therapy for advanced disease.
• Participants that are known to be epidermal growth factor (EGFR)-activating mutation positive must have received an EGFR inhibitor.
• Participants known to be anaplastic lymphoma kinase (ALK)-fusion/rearrangement mutation positive must have received an ALK inhibitor.
• Most prior therapies and prior targeted therapy are allowed and these specific therapies are detailed in the protocol.
• Life expectancy - =/\> 3 months, Eastern Cooperative Oncology Group status = 0 or 1.
• Negative urine or serum pregnancy test within 7 days before Day 1 (first dose of study medication) if female participants is of childbearing potential (WOCBP).
• Men and women agreement to use effective contraceptive method. For WOCBP and for men, agreement to use an effective contraceptive method from the time of screening throughout the study until 1 month for WOCBP or 6 months for men after administration of the last dose of any study medication.
• Specific ranges/levels of Screening labs that are acceptable per protocol.
• Age \>/= 18 years.

You may not qualify if:

• Previous treatment with docetaxel.
• Failed more than 3 treatment regimens for locally advanced or metastatic NSCLC.
• New York Heart Assoc Class III or IV cardiac disease, myocardial infarction within the past 12 months before screening, or pre-existing atrial fibrillation.
• History of cerebrovascular accident or transient ischemic attack.
• Pre-existing carotid artery disease.
• Previous history of pulmonary embolism or pulmonary embolism found on screening exam.
• No ongoing requirement for corticosteroids
• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy at time of screening.
• Known infection with HIV and active infection with hepatitis B or C.
• Known allergy to hyaluronidase or any constituents of docetaxel formulation.
• Current use (within 10 days of day 1) of megestrol acetate.
• Chronic concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole).
• Women currently pregnant or breast feeding.
• Intolerance to dexamethasone, as determined by Investigator.
• History of another primary cancer within the last 3 years that required treatment, with the exception of non-melanoma skin cancer, early stage prostate cancer, or curatively treated cervical carcinoma in situ.

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (8)

California Cancer Associates for Research and Excellence (cCare)

Encinitas, California, 92024, United States

Location

California Cancer Associates for Research and Excellence (cCare)

Fresno, California, 93720, United States

Location

Moores UCSD Cancer Center, Clinical Trials Office

San Diego, California, 92093, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28112, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718-2566, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Heineman T, Baumgart M, Nanavati C, Gabrail N, Van Wart SA, Mager DE, Maneval DC, Fathallah AM, Sekulovich RE. Safety and pharmacokinetics of docetaxel in combination with pegvorhyaluronidase alfa in patients with non-small cell lung cancer. Clin Transl Sci. 2021 Sep;14(5):1875-1885. doi: 10.1111/cts.13041. Epub 2021 Jul 30.

  PMID: 33982408 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Recurrence

Interventions

PEGPH20; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

This study was discontinued early by the Sponsor during the Dose Escalation Period.

Results Point of Contact

• Title: Halozyme Study Information
• Organization: Halozyme, Inc.

medinfo@halozyme.com

1-844-855-4256

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: The study was planned to include a Dose Escalation portion utilizing a standard 3 + 3 dose escalation design. Participants were enrolled sequentially into their assigned dose cohort. The Treatment Period consisted of 21-day treatment cycles with administration of PEGPH20 on Day 1 (doses tested were 1.6, 3.0, and 2.2 ug/kg) and docetaxel (standard dosing 75 mg/m\^2 for all participants) on Day 2 of each cycle.

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: January 27, 2015
• Study Start: February 10, 2015
• Primary Completion: August 9, 2016
• Study Completion: November 14, 2016
• Last Updated: February 8, 2019
• Results First Posted: February 8, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)