A Study of BLZ945 Single Agent or BLZ945 in Combination With PDR001 in Advanced Solid Tumors

NCT02829723 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CBLZ945X21012015-005806-12
• Study Type: interventional
• Target: 192
• Locations: 8 countries
• Sites: 14

Brief Summary

The purpose of this first-in-human (FIH) study of BLZ945 given as a single agent or in combination with PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of BLZ945, administered orally, as a single agent or in combination with PDR001, administered intravenously (i.v.) in adult patients with advanced solid tumors.

Conditions

Advanced Solid Tumors

Keywords

Phase I/II; BLZ945; PDR001; CSF-1R; PD-1; advanced solid tumors; glioblastoma

Outcome Measures

Primary Outcomes (8)

• Phase I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period

  Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.

  From first dose of study medication up to 30 days after last dose, with a maximum duration of 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

• Phase I: Number of Participants With Dose Reductions and Dose Interruptions of BLZ945

  Number of participants with at least one dose reduction of BLZ945 and number of participants with at least one dose interruption of BLZ945.

  From first dose of study medication up to last dose, with a maximum duration of 3 years for BLZ945 single agent and 4 years for BLZ945 in combination with PDR001

• Phase I: Number of Participants With Dose Reductions and Dose Interruptions of PDR001

  Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose reductions were not permitted for PDR001.

  From first dose of study medication up to last dose, with a maximum duration of 4 years

• Phase I: Dose Intensity of BLZ945

  Dose intensity of BLZ945 was calculated as cumulative actual dose in milligrams divided by the number of dose days scheduled per protocol during the treatment period. The denominator was calculated considering that patients received doses 7 days out of every 14 in the 7 days on/7 days off regimen, 4 days out of every 14 in the 4 days on/10 days off regimen and 1 day out of every 7 in the Q1W regimen.

  From first dose of study medication up to last dose, with a maximum duration of 3 years for BLZ945 single agent and 4 years for BLZ945 in combination with PDR001

• Phase I: Dose Intensity of PDR001

  Dose intensity of PDR001 was calculated as cumulative actual dose in milligrams divided by the number of dose days scheduled per protocol during the treatment period. The denominator was calculated considering that patients received doses 1 day out of every 28 in the Q4W regimen.

  From first dose of study medication up to last dose, with a maximum duration of 4 years

• Phase I: Number of Participants With Dose-Limiting Toxicities (DLTs) (Non-Japanese Cohort)

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with BLZ945 as single agent or in combination with PDR001 during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

  28 days

• Phase I: Number of Participants With Dose-Limiting Toxicities (DLTs) (Japanese Cohort)

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with BLZ945 as single agent or in combination with PDR001 during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

  28 days

• Phase II: Progression-Free Survival Rate at 6 Months (PFS6) Per RANO Criteria for Glioblastoma

  PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment per Response Assessment in Neuro Oncology (RANO) criteria. PFS was analyzed using Kaplan-Meier estimates.

  6 months

Secondary Outcomes (41)

• Phase I: Progression-Free Survival (PFS) Per RECIST v1.1

  From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

• Phase I: Progression-Free Survival (PFS) Per irRC

  From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

• Phase I: Progression-Free Survival (PFS) Per RANO

  From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

• Phase I and II: Progression-Free Survival (PFS) Per iRANO

  From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

• Phase I: Progression-Free Survival (PFS) Per Guidelines for Efficacy Evaluation in Lymphoma Studies

  From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

Study Arms (2)

BLZ945 single agent

EXPERIMENTAL

BLZ945 administered as single agent

Drug: BLZ945

BLZ945 + PDR001

EXPERIMENTAL

BLZ945 administered in combination with PDR001

Drug: BLZ945; Drug: PDR001

Interventions

BLZ945 DRUG

BLZ945 administered orally as a capsule. Up to five alternative dosing schedules were evaluated: once per day (QD) 7 days on/7 days off (i.e., administer BLZ945 for 7 days and suspend for 7 days), QD 4 days on/10 days off, twice per day (BID) 4 days on/10 days off, once weekly (Q1W) QD and Q1W BID. Each cycle consisted of 28 days.

BLZ945 + PDR001; BLZ945 single agent

PDR001 DRUG

PDR001 400 mg administered via intravenous (i.v.) infusion every 4 weeks (Q4W)

Also known as: spartalizumab

BLZ945 + PDR001

Eligibility Criteria

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

You may qualify if:

• Phase I: Patients with advanced/metastatic solid tumors including relapsed or refractory (r/r) glioblastoma and r/r lymphoma, with measurable or unmeasurable disease as determined by the respective response evaluation criteria.
• Phase I: Patients with a site of disease amenable to biopsy, and willing to undergo a new tumor biopsy at screening, and during treatment.
• Phase II: Patients with advanced/metastatic/recurrent isocitrate dehydrogenase (IDH) wild-type glioblastoma, with at least one measurable lesion as determined by RANO

You may not qualify if:

• History of severe hypersensitivity reactions to monoclonal antibodies.
• Impaired cardiac function or clinically significant cardiac disease.
• Active autoimmune disease or a documented history of autoimmune disease.
• Systemic steroid therapy or any immunosuppressive therapy
• Use of any vaccines against infectious diseases within 4 weeks of initiation of study treatment.
• Patient receiving treatment with medications that either strong inducers or inhibitors of CYP2C8 or CYP3A4/5, or patients receiving medication that prohibits proton pump inhibitors and that cannot be discontinued at least 1 week prior to start of treatment and for the duration of the study.
• Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the prior 2 weeks before start of study treatment (not applicable for glioblastoma).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (14)

Dana Farber Cancer Institute Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Sarah Cannon Research Institute Sarah Cannon Research

Nashville, Tennessee, 37203, United States

Location

UT M.D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Mays Cancer Ctr Uthsa Mdacc

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 466 8560, Japan

Location

Novartis Investigative Site

Koto Ku, Tokyo, 135 8550, Japan

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

4-(2-(2-hydroxycyclohexylamino)benzothiazol-6-yloxy)pyridine-2-carboxylic acid methylamide; spartalizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: July 12, 2016
• Study Start: October 21, 2016
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: January 18, 2024
• Results First Posted: January 18, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

US (4); IT (1); JP (2); SG (1); TW (1); IL (1); CH (1); ES (3)