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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02829723

Collaborator

(none)

198

Enrollment

Locations

Arms

69.8

Anticipated Duration (Months)

14.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this first-in-human (FIH) study of BLZ945 given as a single agent or in combination with PDR001 is 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.

Dose escalation will be guided by a Bayesian logistic regression model with overdose control. Once MTD/ RP2D is declared, glioblastoma patients will be enrolled in the phase II part to further assess the preliminary anti-tumor activity of BLZ945 as single agent and in combination with PDR001.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: BLZ945 Drug: PDR001	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

198 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II, Open-label, Multi-center Study of the Safety and Efficacy of BLZ945 as Single Agent and in Combination With PDR001 in Adults Patients With Advanced Solid Tumors

Actual Study Start Date :

Oct 21, 2016

Anticipated Primary Completion Date :

Aug 15, 2022

Anticipated Study Completion Date :

Aug 15, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BLZ945 single agent	Drug: BLZ945
Experimental: BLZ945 + PDR001	Drug: BLZ945 Drug: PDR001

Arm

Intervention/Treatment

Experimental: BLZ945 single agent

Drug: BLZ945

Experimental: BLZ945 + PDR001

Drug: BLZ945

Drug: PDR001

Outcome Measures

Primary Outcome Measures

Incidence of Dose limiting toxicities (Phase I) [5 years]
To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
Incidence of Adverse Events (Phase I) [5 years]
To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
Incidence of Serious Adverse Events (Phase I) [5 years]
To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
Dose interruptions (Phase I) [5 years]
To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
Dose reductions (Phase I) [5 years]
To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
Dose intensity (Phase I) [5 years]
To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
Progression-free survival probability (PFSP) at 6 months (Phase II) [6 months]
Percentage of participants with Progression Free Survival (PFS) at 6 months per RANO criteria

Secondary Outcome Measures

Progression Free Survival (PFS) (Phase I) [5 years]
Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO
Best Overall Response (BOR) (Phase I) [5 years]
Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO
Disease Control Rate (DCR) (Phase I) [5 years]
Evaluation is based on RECISTv1.1 or RANO
PFS (Phase II) [5 years]
Evaluation is based on iRANO
BOR (Phase II) [5 years]
Evaluation is based on RANO or iRANO
Duration Of Response (DOR) (Phase II) [5 years]
Evaluation is based on RANO or iRANO
DCR (Phase II) [5 years]
Evaluation is based on RANO or iRANO
Overall Survival (OS) (Phase II) [6 years]
every 12 weeks until end of study
Incidence of AEs (Phase II) [5 years]
Incidence of SAEs (Phase II) [5 years]
Assessment to be completed at least every 28 days
Pharmacokinetics (PK) Area Under the Curve (AUC) (BLZ945 single agent) [5 years]
PK AUC (BLZ945 + PDR001) [5 years]
PK Time of maximum concentration observed (Tmax) (BLZ945 single agent) [5 years]
PK Tmax (BLZ945 + PDR001) [5 years]
PK peak serum concentration (Cmax) (BLZ945 + PDR001) [5 years]
PK Cmax (BLZ945 single agent) [5 years]
Concentration of anti-PDR001 antibodies (BLZ945 + PDR001) [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Phase I: Patients with advanced/metastatic solid tumors, with measurable or unmeasurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
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

Other protocol defined inclusion criteria may apply

Exclusion Criteria:

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.

Other protocol defined exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
2	Sarah Cannon Research Institute Sarah Cannon Research	Nashville	Tennessee	United States	37203
3	UT M.D Anderson Cancer Center	Houston	Texas	United States	77030
4	Cancer Therapy and Research Center UT Health Science Center	San Antonio	Texas	United States	78229
5	Novartis Investigative Site	Tel Aviv		Israel	6423906
6	Novartis Investigative Site	Rozzano	MI	Italy	20089
7	Novartis Investigative Site	Nagoya	Aichi	Japan	466 8560
8	Novartis Investigative Site	Koto ku	Tokyo	Japan	135 8550
9	Novartis Investigative Site	Singapore		Singapore	169610
10	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
11	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
12	Novartis Investigative Site	Madrid		Spain	28041
13	Novartis Investigative Site	Zurich		Switzerland	8091
14	Novartis Investigative Site	Taipei		Taiwan	10002