Have you or your loved ones been diagnosed with advanced solid tumors?
You may be eligible to participate in a advanced solid tumors clinical trial.
Have you or your loved ones been diagnosed with advanced solid tumors? You may be eligible to participate in a advanced solid tumors clinical trial.
What is a clinical trial? Is participating in a clinical trial right for you? Learn more
Have you or your loved ones been diagnosed with advanced solid tumors?
You may be eligible to participate in a advanced solid tumors clinical trial.
Have you or your loved ones been diagnosed with advanced solid tumors? You may be eligible to participate in a advanced solid tumors clinical trial.
Active not recruiting
Male & Female
18 Years +
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.
Details for the study
Brief Title
A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors
Official Title
A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-181 as Monotherapy and in Combination With Another Anti-Cancer Therapy in Subjects With Advanced Solid Tumors
Brief Summary
This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 <br /> dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) <br /> profile of budigalimab. This study will also evaluate the safety and tolerability of <br /> budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with <br /> venetoclax. The study will consist of 3 parts: budigalimab monotherapy dose escalation and <br /> expansion, budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in <br /> combination with venetoclax.
Treatments and/or Procedures
ABBV 181
Intravenous infusion
Rovalpituzumab tesirine
Intravenous infusion
Venetoclax
Tablet taken orally
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
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.
Primary
Part 3: Time to Cmax (Tmax) of Venetoclax
Time to maximum plasma concentration of of Venetoclax
Primary
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.
Primary
Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab
Terminal phase elimination half-life (t1/2) of Budigalimab
Primary
Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab
Maximum Serum Concentration (Cmax) of Budigalimab
Primary
Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab
Time to maximum plasma concentration of Budigalimab
Primary
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.
Primary
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.
Primary
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.
Primary
Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax
Maximum Serum Concentration (Cmax) for Venetoclax
Primary
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
Primary
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
Secondary
Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine
Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine
Secondary
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
Secondary
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
Secondary
Part 2: Time to Cmax (Tmax) of Budigalimab
Time to maximum plasma concentration of Budigalimab
Secondary
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.
Secondary
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.
Secondary
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.
Secondary
Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine
Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine
Secondary
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.
Secondary
Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine
Time to maximum plasma concentration of Rovalpituzumab Tesirine
Secondary
Part 2: Terminal Half-life (t1/2) of Budigalimab
Terminal phase elimination half-life (t1/2) of Budigalimab
Study Criteria
Inclusion Criteria: - Participant must have an advanced solid tumor and must not be a candidate for surgical resection or other approved therapeutic regimen known to provide clinical benefit. For dose escalation, the participant may have been previously treated with a programmed cell death 1 (PD-I) targeting agent. For dose expansion, the participant must be PD-I/PD-L1 targeting agent naïve. For Part 2 budigalimab in combination with rovalpituzumab tesirine, the participant must have SCLC with progressive disease and have failed platinum containing therapy and be PD-1/PD-L1 targeting agent naïve. For Part 3 budigalimab in combination with venetoclax, the participant must have locally advanced or metastatic NSCLC and received 1 to 4 prior lines of therapy in the advanced or metastatic setting including 1 regimen that included a PD-1 or PD-L1 targeting agent which was discontinued following disease progression. Participants who are naïve to treatment with a PD-1/PD-L1 targeting agent OR who have received more than 1 regimen containing a PD-1/PD-L1 targeting agent are NOT eligible for Part 3. - Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for the monotherapy cohort and an ECOG 0 to 1 for budigalimab in combination with rovalpituzumab tesirine cohort (Part 2) and budigalimab in combination with venetoclax (Part 3). - Participants have adequate bone marrow, renal, hepatic and coagulation function. - Participants must have measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the dose escalation portion of the trial. Participants in the expansion cohort must have measurable disease per RECIST version 1.1 or disease evaluable by assessment of tumor antigens. Participants enrolled in budigalimab in combination with venetoclax cohort (Part 3) must have measurable disease per RECIST version 1.1. Exclusion Criteria: - Participant has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, small molecule, herbal therapy, or any investigational therapy within a period of 5 half-lives, prior to the first dose of budigalimab or Rovalpituzumab Tesirine or venetoclax. - For budigalimab in combination with rovalpituzumab tesirine cohort (Part 2), participant must not have had prior exposure to Rovalpituzumab Tesirine or a pyrrolobenzodiazepine (PBD) based drug. - Participant has unresolved adverse events greater than grade 1 from prior anticancer therapy except for alopecia. - Current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions). - History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis. - Confirmed positive test results for human immunodeficiency virus (HIV), or participants with chronic or active hepatitis A, B or C. Participants who have a history of hepatitis B or C who have undetectable hepatitis B (HBV) DNA or hepatitis C (HCV) RNA after anti-viral therapy may be enrolled. - Participant has known history or inflammatory bowel disease, pneumonitis, or known uncontrolled metastases to the central nervous system (CNS) (with certain exceptions). - Participants with a history of or ongoing pneumonitis or interstitial lung disease are also excluded. - For budigalimab plus venetoclax therapy (Part 3), participant must not receive a strong or moderate inducer or inhibitor of cytochrome P450 (CYP)3A within 7 days before first venetoclax dose. - For budigalimab plus venetoclax therapy (Part 3), participants with a known gastrointestinal disorder (i.e.: malabsorption syndrome), complication (i.e.: dysphagia) or surgery that could make consumption or absorption of oral medication problematic are also excluded. - All Cohorts: Participants with a history of Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS)