Clinical trial NCT03150810: Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors
Official title: A Phase 1b Study to Assess the Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Subjects With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Solid Tumors
Keywords: Ovarian cancer
Triple negative breast cancer
Small cell lung cancer
Gastric cancer
temozolomide
BGB-290
antineoplastic agents
alkylating, alkylating agents,
Poly (ADP-ribose) polymerase inhibitors
enzyme inhibitors
Head and neck cancer
Esophageal cancer
Soft tissue sarcoma
Non small cell lung cancer
pamiparib
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
Collaborators: name: Myriad Genetics, Inc.
First posted: 2017-05-12
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to determine the safety and tolerability of pamiparib, the maximum tolerated dose (MTD) or maximum administered dose (MAD) for pamiparib combined with TMZ, to select the recommended Phase 2 dose (RP2D) and schedule of pamiparib in combination with TMZ, and to determine the antitumor activity of pamiparib in combination with TMZ.


Eligibility criteria: Key Inclusion Criteria:

1. Age ≥18 years old with advanced or metastatic stage solid tumors
2. Eastern Cooperative Oncology Group (ECOG) status ≤ 1
3. Have disease either evaluable (dose-escalation cohort) or measurable (dose-escalation and -expansion cohorts) per RECIST V1.1, except for prostate cancer participants
4. Agree to provide archival tumor tissue
5. Additional inclusion criteria for dose expansion cohorts:

   * Participants with homologous recombination deficiency (HRD+) or known BRCA mutant ovarian cancer Previously received at least one line of platinum-containing therapy in the advanced or metastatic setting and No progression or recurrent disease within 6 months from last platinum-containing regimen.
   * Participants with HRD+ or known BRCA mutant triple-negative breast cancer Up to one prior platinum-containing treatment in any treatment setting and up to 3 prior lines of therapy in the advanced or metastatic setting
   * Participants with HRD+ or known BRCA mutant prostate cancer Chemotherapy-naïve or previously received up to two taxane-based chemotherapy regimens, with documented prostate cancer progression
   * Participants with small cell lung cancer and gastric cancer, previously received ≤ 2 prior lines of therapy
   * Other HRD+ solid tumors of multiple indications

Key Exclusion Criteria: All participants

1. Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.
2. Refractory to platinum-based therapy (dose-expansion cohort).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 5 years and 10 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 5 years and 10 months
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Pamiparib
timeFrame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose (each cycle is 28 days)
measure: Plasma Trough Concentrations of Pamiparib (Ctrough)
timeFrame: Cycle 1 Day 15 predose
measure: Time to Reach Cmax (Tmax) of Pamiparib
timeFrame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.
measure: Area Under the Curve From Time 0 to 4 Hours (AUC0-4h) of Pamiparib
timeFrame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, and 4 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.
measure: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Pamiparib
timeFrame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing
measure: Terminal Elimination Half-life (t1/2) of Pamiparib
timeFrame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
measure: Apparent Clearance (CL/F) of Pamiparib
timeFrame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
measure: Apparent Volume of Distribution During Terminal Phase (Vz/F) of Pamiparib
timeFrame: 2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days)
measure: Plasma Concentration of Temozolomide (TMZ)
timeFrame: Predose (within 30 min prior to dose) and 1 hour post dose on Cycle 1 Day 1 and Cycle 1 Day 7
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 5 years and 10 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 5 years and 10 months
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 5 years and 10 months)
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years and 10 months
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: Start Midwest
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Park At Eastchester Einstein Campus
state: New York
city: New York
country: United States
facility: Mount Sinai Prime
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology (Loop) Usor
state: Texas
city: Houston
country: United States
facility: The University of Texas Md Anderson Cancer Center
state: Texas
city: Camperdown
country: Australia
facility: Chris Obrien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: Saint Vincents Hospital Sydney
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Centre South Brisbane
state: Queensland
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Barcelona
country: Spain
facility: Ico H Duran I Reynals
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Start Madrid Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de La Macarena
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: High Heaton
country: United Kingdom
facility: Northern Centre For Cancer Care
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute Uk
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: