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

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: BLZ945; Drug: PDR001

Detailed Description

This study was a first in human, open-label, multi-center phase I/II study which consisted of a phase I dose escalation part of BLZ945 as single agent, and of BLZ945 in combination with PDR001, where alternative dosing regimens of BLZ945 were evaluated. The escalation was guided by a Bayesian logistic regression model with overdose control. Once the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) for BLZ945 as single agent was established, a phase II part could commence, should signs of antitumor activity had been seen during the phase I. Once the MTD/RP2D for BLZ945 in combination with PDR001 was established, a phase II part could commence.

Phase I part of the study involved patients with advanced solid tumors, including patients with recurrent glioblastoma and patients with Hodgkin's lymphoma, and phase II part patients with relapsed or refractory glioblastoma.

A separate Japanese single agent dose escalation was performed in order to ensure that the safety and pharmacokinetic profiles of BLZ945 single agent were adequately characterized in Japanese patients. The Japanese dose escalation for BLZ945 single agent run separately from the ongoing global dose escalation. No Japanese patients were enrolled in phase II part according to protocol. The enrollment of the Japanese cohort was halted per investigator letter, dated 18-Jun-2021.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 466 8560
      • Novartis Investigative Site
  • Tokyo
    • Koto ku, Tokyo, Japan, 135 8550
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 168583
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Hospitalet de LLobregat, Catalunya, Spain, 08907
      • Novartis Investigative Site
• Switzerland
  • Zurich, Switzerland, 8091
    • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute Dana Farber Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute Sarah Cannon Research
  • Texas
    • Houston, Texas, United States, 77030
      • UT M.D Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Ctr Uthsa Mdacc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Phase I: Patients with a site of disease amenable to biopsy, and willing to undergo a new tumor biopsy at screening, and during treatment.
3. Phase II: Patients with advanced/metastatic/recurrent isocitrate dehydrogenase (IDH) wild-type glioblastoma, with at least one measurable lesion as determined by RANO

Exclusion Criteria:

1. History of severe hypersensitivity reactions to monoclonal antibodies.
2. Impaired cardiac function or clinically significant cardiac disease.
3. Active autoimmune disease or a documented history of autoimmune disease.
4. Systemic steroid therapy or any immunosuppressive therapy
5. Use of any vaccines against infectious diseases within 4 weeks of initiation of study treatment.
6. 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.
7. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BLZ945 single agent; BLZ945 administered as single agent	Drug: BLZ945; 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.
Experimental: BLZ945 + PDR001; BLZ945 administered in combination with PDR001	Drug: BLZ945; 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.; Drug: PDR001; PDR001 400 mg administered via intravenous (i.v.) infusion every 4 weeks (Q4W); Other Names: spartalizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Progression-Free Survival (PFS) Per RECIST v1.1	PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. PFS was analyzed using Kaplan-Meier estimates.	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	PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per immune-related Response Criteria (irRC). PFS was analyzed using Kaplan-Meier estimates.	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	PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per response assessment in neuro-oncology (RANO) criteria. PFS was analyzed using Kaplan-Meier estimates.	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	PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per immune response assessment in neuro-oncology (iRANO) criteria. PFS was analyzed using Kaplan-Meier estimates.	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	PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per guidelines for efficacy evaluation in lymphoma studies. PFS was analyzed using Kaplan-Meier estimates.	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: Best Overall Response (BOR) With Confirmation Per RECIST v1.1	BOR is defined as the best response recorded from the start of the study treatment until disease progression/recurrence, based on local investigator assessment per RECIST v1.1. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation. Complete Response (CR) and Partial response (PR) had to be confirmed by a new assessment after at least 4 weeks.	From start of treatment until disease progression, assessed up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase I: Best Overall Response (BOR) With Confirmation Per irRC	BOR is defined as the best response recorded from the start of the study treatment until disease progression/recurrence, based on local investigator assessment per irRC. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation. Complete Response (CR) and Partial response (PR) had to be confirmed by a new assessment after at least 4 weeks. Additionally, for irRC, progressive disease had to be confirmed.	From start of treatment until disease progression, assessed up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase I and II: Best Overall Response (BOR) (Sustained) Per RANO	BOR is defined as the best response recorded from the start of the study treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started), based on local investigator assessment per RANO criteria. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation. If a response recorded at one scheduled magnetic resonance imaging (MRI) did not persist at the next regular scheduled MRI, the response was recorded based on the prior scan, but was designated as a non-sustained response. If the response was sustained, i.e. still present on the subsequent MRI, it was recorded as a sustained response, lasting until the time of tumor progression. CR and PR had to be confirmed by repeat assessments performed not less than 4 weeks after the criteria for response were first met.	From start of treatment until disease progression, assessed up to 4.1 years in Phase I and 1.4 years in Phase II
Phase I and II: Best Overall Response (BOR) (Sustained) Per iRANO	BOR is defined as the best response recorded from the start of the study treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started), based on local investigator assessment per iRANO. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation. If a response recorded at one scheduled magnetic resonance imaging (MRI) did not persist at the next regular scheduled MRI, the response was recorded based on the prior scan, but was designated as a non-sustained response. If the response was sustained, i.e. still present on the subsequent MRI, it was recorded as a sustained response, lasting until the time of tumor progression. CR and PR had to be confirmed by repeat assessments performed not less than 4 weeks after the criteria for response were first met. Additionally, for iRANO, progressive disease had to be confirmed.	From start of treatment until disease progression, assessed up to 4.1 years in Phase I and 1.4 years in Phase II
Phase I: Best Overall Response (BOR) Per Guidelines for Efficacy Evaluation in Lymphoma Studies	BOR is defined as the best response recorded from the start of the study treatment until disease progression/recurrence, based on local investigator assessment per guidelines for efficacy evaluation in lymphoma studies. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation.	From start of treatment until disease progression, assessed up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase I: Overall Response Rate (ORR) Per RECIST v1.1	ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1.	Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase I: Overall Response Rate (ORR) Per irRC	ORR is the percentage of patients with a best overall response of complete response (irCR) or partial response (irPR), based on local investigator assessment per irRC.	Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase I: Overall Response Rate (ORR) Per Guidelines for Efficacy Evaluation in Lymphoma Studies	ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per guidelines for efficacy evaluation in lymphoma studies.	Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase I: Disease Control Rate (DCR) Per RECIST v1.1	DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per RECIST v1.1.	Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase I: Disease Control Rate (DCR) Per irRC	DCR is the percentage of patients with a best overall response of complete response (irCR), partial response (irPR) or stable disease (irSD), based on local investigator assessment per irRC.	Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase I and II: Disease Control Rate (DCR) Per RANO	DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per RANO criteria.	Up to 4.1 years in Phase I and 1.4 years in Phase II
Phase I and II: Disease Control Rate (DCR) Per iRANO	DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per iRANO criteria.	Up to 4.1 years in Phase I and 1.4 years in Phase II
Phase I: Disease Control Rate (DCR) Per Guidelines for Efficacy Evaluation in Lymphoma Studies	DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per guidelines for efficacy evaluation in lymphoma studies.	Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001
Phase II: Duration of Response (DOR) Per RANO	DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RANO. DOR is defined as the time from the date of first documented response to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.	Up to 1.4 years for BLZ945 single agent and 0.6 years for BLZ945 in combination with PDR001
Phase II: Duration of Response (DOR) Per iRANO	DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per iRANO. DOR is defined as the time from the date of first documented response to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.	Up to 1.4 years for BLZ945 single agent and 0.6 years for BLZ945 in combination with PDR001
Phase II: Overall Survival (OS)	OS is defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, OS time was censored at the date of last contact. OS was estimated using Kaplan-Meier estimates.	From start of treatment until death due to any cause, assessed up to 1.9 years for BLZ945 single agent and 1.3 years for BLZ945 in combination with PDR001
Phase II: 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 1.4 years for BLZ945 single agent and 0.6 years for BLZ945 in combination with PDR001
Phase II: 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 1.3 years for BLZ945 single agent and 0.5 years for BLZ945 in combination with PDR001
Phase II: 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 0.5 years
Phase II: 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 4 days out of every 14 in the 4 days on/10 days off regimen.	From first dose of study medication up to last dose, with a maximum duration of 1.3 years for BLZ945 single agent and 0.5 years for BLZ945 in combination with PDR001
Phase II: 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 0.5 years
Phase I and II: Maximum Observed Serum Concentration (Cmax) of BLZ945 (7d on/7d Off Regimen)	Pharmacokinetic (PK) parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.	Cycle 1 Day 1 and Cycle 1 Day 7 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose
Phase I and II: Maximum Observed Serum Concentration (Cmax) of BLZ945 (Q1W Regimen)	Pharmacokinetic (PK) parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.	Cycle 1 Day 1 and Cycle 1 Day 8 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose (QD dosing); pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose (BID dosing)
Phase I and II: Maximum Observed Serum Concentration (Cmax) of BLZ945 (4d on/10d Off Regimen)	Pharmacokinetic (PK) parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.	Cycle 1 Day 1 and Cycle 1 Day 4 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose (QD dosing); pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose (BID dosing)
Phase I and II: Time to Reach Maximum Serum Concentration (Tmax) of BLZ945 (7d on/7d Off Regimen)	Pharmacokinetic (PK) parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.	Cycle 1 Day 1 and Cycle 1 Day 7 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose
Phase I and II: Time to Reach Maximum Serum Concentration (Tmax) of BLZ945 (Q1W Regimen)	Pharmacokinetic (PK) parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.	Cycle 1 Day 1 and Cycle 1 Day 8 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose (QD dosing); pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose (BID dosing)
Phase I and II: Time to Reach Maximum Serum Concentration (Tmax) of BLZ945 (4d on/10d Off Regimen)	Pharmacokinetic (PK) parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.	Cycle 1 Day 1 and Cycle 1 Day 4 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose (QD dosing); pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose (BID dosing)
Phase I and II: Area Under the Serum Concentration-time Curve From Time Zero to 24 Hours Post Dose (AUC0-24hr) of BLZ945 (7d on/7d Off Regimen)	PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-24hr calculation.	Cycle 1 Day 1 and Cycle 1 Day 7 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose
Phase I and II: Area Under the Serum Concentration-time Curve From Time Zero to 24 Hours Post Dose (AUC0-24hr) of BLZ945 (Q1W Regimen, QD Dosing)	PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-24hr calculation.	Cycle 1 Day 1 and Cycle 1 Day 8 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose
Phase I and II: Area Under the Serum Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of BLZ945 (Q1W Regimen, BID Dosing)	PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.	Cycle 1 Day 1 and Cycle 1 Day 8 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose
Phase I and II: Area Under the Serum Concentration-time Curve From Time Zero to 24 Hours Post Dose (AUC0-24hr) of BLZ945 (4d on/10d Off Regimen, QD Dosing)	PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-24hr calculation.	Cycle 1 Day 1 and Cycle 1 Day 4 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose
Phase I and II: Area Under the Serum Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of BLZ945 (4d on/10d Off Regimen, BID Dosing)	PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.	Cycle 1 Day 1 and Cycle 1 Day 4 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose
Phase I and II: Maximum Observed Serum Concentration (Cmax) of PDR001	Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.	pre-infusion and 1, 24, 168, 336 and 672 hours after completion of the infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The average duration of the infusion was 30 minutes. The duration of one cycle was 28 days
Phase I and II: Time to Reach Maximum Serum Concentration (Tmax) of PDR001	Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.	pre-infusion and 1, 24, 168, 336 and 672 hours after completion of the infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The average duration of the infusion was 30 minutes. The duration of one cycle was 28 days
Phase I and II: Area Under the Serum Concentration-time Curve From Time Zero to 28 Days Post Dose (AUC0-28day) of PDR001	PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-28day calculation.	pre-infusion and 1, 24, 168, 336 and 672 hours after completion of the infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The average duration of the infusion was 30 minutes. The duration of one cycle was 28 days
Phase I and II: Number of Participants With Anti-PDR001 Antibodies	Immunogenicity was evaluated in serum in a validated three-tiered assay approach. Samples were screened for potential anti-PDR001 antibodies and positive screen results were confirmed using a confirmatory assay. For confirmed anti-drug antibodies (ADA) positive samples, titers were determined. Patient ADA status was defined as follows: ADA-negative at baseline: ADA-negative sample at baseline; ADA-positive at baseline: ADA-positive sample at baseline; ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline determinant sample, all of which are ADA-negative samples; Treatment-induced ADA-positive = ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample; Treatment-boosted ADA-positive = ADA-positive sample at baseline and at least 1 treatment-boosted ADA-positive sample	Baseline (before first dose) and post-baseline (assessed throughout the treatment and safety follow-up, up to 4.4 years in phase I and 0.9 years in phase II).

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2016
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: July 8, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (Estimated): July 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: advanced solid tumors; PD-1; CSF-1R; glioblastoma; Phase I/II; PDR001; BLZ945
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Spartalizumab
• Other Study ID Numbers: CBLZ945X2101; 2015-005806-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No