A Study of ABBV-428, an Immunotherapy, in Subjects 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 ABBV-428 when administered as monotherapy or in combination with nivolumab in participants with advanced solid tumors.

Official Title
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A Multi-Center, Phase 1, Open-Label, Dose-Escalation Study of ABBV-428, an Immunotherapy in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors Cancer

Intervention / Treatment
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* Drug: ABBV-428
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have an advanced solid tumor that has progressed on standard therapies known to provide clinical benefit or the participants are intolerant to such therapies. Participants have adequate bone marrow, renal, hepatic and coagulation function. For all dose expansion arms, participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Participants in combination therapy cohorts must have an advanced solid tumor where the use of nivolumab is standard therapy. Exclusion Criteria: Active or prior documented autoimmune disease in the last 2 years. Participants with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. 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 B or C. Participants who have a history of hepatitis B or C who have undetectable HBV DNA or HCV RNA after anti-viral therapy may be enrolled. Prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis (or any other unresolved or symptomatic adverse event in the last 3 months) while receiving immunotherapy. Male participants who are considering fathering a child or donating sperm during the study or for at least 3 or 5 months (for monotherapy and combination therapy participants, respectively) after the last dose of study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>ABBV-428 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). | Drug: ABBV-428<br>* ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.<br>|
| Experimental: Arm A, B, and C<br>Additional participants (with ovarian cancer, NSCLC, etc.) will be enrolled in a dose expansion cohorts that will further evaluate ABBV-428. | Drug: ABBV-428<br>* ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.<br>|
| Experimental: Arm D<br>Additional participants with NSCLC will be enrolled in an expansion cohort that will further evaluate ABBV-428 plus nivolumab. | Drug: ABBV-428<br>* ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.<br>Drug: Nivolumab<br>* Nivolumab will be administered by intravenous infusion according to approved dose and dosing schedules.<br>* Other names: OPDIVO;|
| Experimental: Arm 2<br>ABBV-428 plus nivolumab. | Drug: ABBV-428<br>* ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.<br>Drug: Nivolumab<br>* Nivolumab will be administered by intravenous infusion according to approved dose and dosing schedules.<br>* Other names: OPDIVO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | First dose of study drug through at least 100 days after end of treatment; up to 2 years after last participants first dose | 
| Recommended Phase 2 Dose (RPTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab | If a maximum tolerated dose (MTD) is reached, the RPTD of ABBV-428 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 pharmacokinetic data. | 1 day of study drug administration within the 28-day cycle at the designated cohort dose | 
| Area under the serum concentration-time curve (AUC) of ABBV-428 |  | Up to 30 days after a 24-month treatment period | 
| Terminal half-life (t1/2) of ABBV-428 |  | Up to 30 days after a 24-month treatment period | 
| Maximum observed serum concentration (Cmax) of ABBV-428 |  | Up to 30 days after a 24-month treatment period | 
| Maximum tolerated dose (MTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab | The highest dose level at which less than 2 of 6 participants or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity. | Up to 2 years | 
| Time to Cmax (Tmax) of ABBV-428 |  | Up to 30 days after a 24-month treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Objective Response (DOR) | DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first. | Up to 30 days after a 24-month of treatment period | 
| Clinical benefit rate (CBR) | CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease for at least 24 weeks to the treatment. | Up to 30 days after a 24-month of treatment period | 
| Progression-Free Survival (PFS) | PFS time is defined as the time from the first dose of ABBV-428 to disease progression or death, whichever occurs first | Up to 30 days after a 24-month of treatment period | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment. | Up to 30 days after a 24-month of treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Neoplasm, Advanced solid tumor, Nivolumab, Non-small cell lung cancer (NSCLC), Non-squamous NSCLC, Ovarian cancer