This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of budigalimab. This study will also evaluate the safety and tolerability of budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax. The study will consist of 3 parts: budigalimab monotherapy dose escalation and expansion, budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
182
Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab
If a maximum tolerated dose (MTD) is reached, the RPTD of budigalimab will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and other available data.
Time frame: Up to 6 months
Part 1: Maximum tolerated dose (MTD) of Budigalimab
MTD will be defined at the highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.
Time frame: Up to 6 months
Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab
Terminal phase elimination half-life (t1/2) of Budigalimab
Time frame: Up to 4 Weeks
Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab
Maximum Serum Concentration (Cmax) of Budigalimab
Time frame: Up to 12 Weeks
Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab
Time to maximum plasma concentration of Budigalimab
Time frame: Up to 12 Weeks
Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab
Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab
Time frame: Up to 12 Weeks
Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination
The safety and tolerability of a single dose of Budigalimab in combination with Rovalpituzumab Tesirine will be assessed in patients with advanced small cell lung cancer (SCLC) to determine the RPTD and schedule for the combination.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Moores Cancer Center at UC San Diego /ID# 157374
La Jolla, California, United States
The University of Chicago Medical Center /ID# 157375
Chicago, Illinois, United States
Carolina BioOncology Institute /ID# 157376
Huntersville, North Carolina, United States
South Texas Accelerated Research Therapeutics /ID# 157378
San Antonio, Texas, United States
Virginia Cancer Specialists - Fairfax /ID# 157377
Fairfax, Virginia, United States
Blacktown Hospital /ID# 167386
Blacktown, New South Wales, Australia
St Vincent's Hospital Melbourne /ID# 167552
Fitzroy Melbourne, Victoria, Australia
Linear Clinical Research /ID# 170797
Nedlands, Western Australia, Australia
Medizinische Universitaet Graz /ID# 168752
Graz, Styria, Austria
Universitair Ziekenhuis Antwerpen /ID# 170702
Edegem, Antwerpen, Belgium
...and 16 more locations
Time frame: Up to 6 Months
Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination.
The safety and tolerability of Budigalimab in combination with venetoclax will be assessed in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) to determine the RPTD for the combination.
Time frame: Up to 6 Months
Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax
Maximum Serum Concentration (Cmax) for Venetoclax
Time frame: Up to 12 Weeks
Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax
Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24)) of Venetoclax
Time frame: Up to 12 Weeks
Part 3: Time to Cmax (Tmax) of Venetoclax
Time to maximum plasma concentration of of Venetoclax
Time frame: Up to 12 Weeks
Part 1, Part 2, Part 3: Number of Participants with Adverse Events
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Time frame: From first dose of study drug until 90 days following last dose of study drug (up to 24 months)
Part 2: Terminal Half-life (t1/2) of Budigalimab
Terminal phase elimination half-life (t1/2) of Budigalimab
Time frame: Up to 4 Weeks
Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine
Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine
Time frame: Up to 4 Weeks
Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine
Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine
Time frame: Up to 12 Weeks
Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine
Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Rovalpituzumab Tesirine
Time frame: Up to 12 Weeks
Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab
Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab
Time frame: Up to 12 Weeks
Part 2: Time to Cmax (Tmax) of Budigalimab
Time to maximum plasma concentration of Budigalimab
Time frame: Up to 12 Weeks
Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine
Time to maximum plasma concentration of Rovalpituzumab Tesirine
Time frame: Up to 12 Weeks
Part 1 and Part 3: Objective response rate (ORR)
ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.
Time frame: First dose of study drug through at least 30 days after last dose of study drug.
Part 1 and Part 3: Clinical benefit rate (CBR, defined as CR, PR or SD)
CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.
Time frame: First dose of study drug through at least 30 days after last dose of study drug.
Part 1 and Part 3: Progression-free survival (PFS)
PFS time is defined as the time from the participant's first dose of study drug (Day 1) to either the participant's disease progression or death, whichever occurs first.
Time frame: First dose of study drug through at least 30 days after last dose of study drug.
Part 1, Part 2 and Part 3: Duration of objective response (DOR)
DOR for a participant is defined as the time from the participant's initial objective response to study drug therapy to disease progression or death, whichever occurs first.
Time frame: First dose of study drug through at least 30 days after last dose of study drug.