A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Venetoclax
* Drug: Rovalpituzumab Tesirine
* Drug: ABBV-181


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABBV-181 plus Venetoclax<br>Venetoclax will be taken once daily beginning 7 days prior to cycle 1 and continuing daily for a 28 day cycle and ABBV-181 will be administered every 4 weeks. | Drug: Venetoclax<br>* Tablet taken orally<br>Drug: ABBV-181<br>* Intravenous infusion<br>* Other names: Budigalimab;|
| Experimental: ABBV-181<br>ABBV-181 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). Based on available safety, pharmacokinetic, and pharmacodynamic data from the dose-escalation part of the study, participants will be enrolled in dose-expansion cohorts to further evaluate ABBV-181 at a dose level which is at or below the Maximum tolerated dose (MTD). In the Monotherapy Expansion portion of the study, ABBV-181 will be administered in 28-day dosing cycles at either 1 dose per cycle or 2 doses per cycle. Based on available safety, PK and PD data from the single agent dose-escalation part of the study, a dose for ABBV-181 will be selected to evaluate in combination with Rovalpituzumab Tesirine or venetoclax. | Drug: ABBV-181<br>* Intravenous infusion<br>* Other names: Budigalimab;|
| Experimental: ABBV-181 plus Rovalpituzumab Tesirine<br>Rovalpituzumab Tesirine will be given once every six weeks times two doses and ABBV-181 will be administered every 3 weeks. | Drug: Rovalpituzumab Tesirine<br>* Intravenous infusion<br>Drug: ABBV-181<br>* Intravenous infusion<br>* Other names: Budigalimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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 | Up to 4 Weeks | 
| Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab | Maximum Serum Concentration (Cmax) of Budigalimab | Up to 12 Weeks | 
| Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab | Time to maximum plasma concentration of Budigalimab | 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 | 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. | 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. | Up to 6 Months | 
| Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax | Maximum Serum Concentration (Cmax) for Venetoclax | 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 | Up to 12 Weeks | 
| Part 3: Time to Cmax (Tmax) of Venetoclax | Time to maximum plasma concentration of of Venetoclax | 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. | From first dose of study drug until 90 days following last dose of study drug (up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Terminal Half-life (t1/2) of Budigalimab | Terminal phase elimination half-life (t1/2) of Budigalimab | Up to 4 Weeks | 
| Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine | Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine | Up to 4 Weeks | 
| Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine | Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine | 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 | 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 | Up to 12 Weeks | 
| Part 2: Time to Cmax (Tmax) of Budigalimab | Time to maximum plasma concentration of Budigalimab | Up to 12 Weeks | 
| Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine | Time to maximum plasma concentration of Rovalpituzumab Tesirine | 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. | 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. | 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. | 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. | First dose of study drug through at least 30 days after last dose of study drug. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Budigalimab, Cancer, Advanced Solid Tumors, Non-small cell lung cancer (NSCLC), Triple negative breast cancer, Ovarian cancer, Hepatocellular carcinoma, Gastric cancer, Small cell lung cancer, Mesothelioma, Cholangiocarcinoma, Merkel cell carcinoma, Head and neck cancer