A Study of ABBV-927 and ABBV-181, an Immunotherapy, in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of ABBV-927, and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 in participants with advanced solid tumors.

Official Title
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A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-927 and ABBV-181, 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-927
* Drug: ABBV-927
* Drug: ABBV-181


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. Participants have adequate bone marrow, kidney and liver function. Participants with a history of chronic heart failure or significant cardiovascular disease must have an echocardiogram or multigated acquisition scan indicating left ventricular ejection fraction greater than or equal to 45% within 28 days prior to the first dose of study drug. Participants must have creatinine clearance greater than or equal to 50 mL/min as measured by 24-hour urine or estimated by the Cockcroft-Gault formula. Participants must have total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase and alanine aminotransferase less than or equal to 2.5 times ULN. Participants in all monotherapy arms 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 in all combination therapy arms must have recurrent or metastatic HNSCC or NSCLC and previously received platinum-based therapy and progressed either during or after anti-programmed death ligand 1 (PDL1)-based therapy. In addition, participants must have received only one prior immunotherapy. The Sponsor may decide to limit the specific tumor types selected or treatment settings for specific arms based on evidence gathered. Exclusion Criteria: Participant must not have an active or prior documented autoimmune disease in the last 2 years. Participant must not have current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions). Participant must not have a history of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, previous clinical diagnosis of tuberculosis, inflammatory bowel disease, interstitial lung disease, or immune-mediated pneumonitis. Participant must not have a history of clinically significant uncontrolled condition(s) including but not limited to the following: uncontrolled hypertension; symptomatic congestive heart failure; unstable angina pectoris or cardiac arrhythmia including atrial fibrillation. Participant must not have a history of coagulopathy or a platelet disorder associated with significant clinical risk of thromboembolic event in the judgement of the investigator, or major thromboembolic event within 6 months prior to the first dose of study treatment. Participant must not have a prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis while receiving immunotherapy. Participant must not have a known uncontrolled malignancy of the central nervous system. Participants in all combination therapy arms must not have a history of exposure to an immunotherapy experiencing an immune-mediated adverse event that required permanent discontinuation of the immunotherapy. Female participants must not be pregnant, breastfeeding or considering becoming pregnant 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. Male participants must not be 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. Participant is judged by the investigator to have evidence of hemolysis. For Japan only, participants with a history of interstitial lung disease (pneumonitis) or current interstitial lung disease (pneumonitis).

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: Escalating Arm 1: ABBV-927<br>Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927. | Drug: ABBV-927<br>* Intravenous<br>|
| Experimental: Escalating Arm 2: ABBV-927<br>Participants with solid tumors will receive escalating intratumoral (IT) doses of ABBV-927. | Drug: ABBV-927<br>* Intratumoral<br>|
| Experimental: Escalating Arm 3: ABBV-927+ABBV-181<br>Participants with Non-Small Cell Lung Cancer (NSCLC) will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181. | Drug: ABBV-927<br>* Intravenous<br>Drug: ABBV-181<br>* Intravenous<br>* Other names: Budigalimab;|
| Experimental: Escalating Arm 4: ABBV-927+ABBV-181<br>Participants with Head and Neck Squamous Cell Carcinoma (HNSCC) will receive escalating IT doses of ABBV-927 and IV doses of ABBV-181. | Drug: ABBV-927<br>* Intratumoral<br>Drug: ABBV-181<br>* Intravenous<br>* Other names: Budigalimab;|
| Experimental: Escalating Arm 5 (Japan): ABBV-927<br>Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927. | Drug: ABBV-927<br>* Intravenous<br>|
| Experimental: Escalating Arm 6 (Japan): ABBV-927+ABBV-181<br>Participants with solid tumors will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181. | Drug: ABBV-927<br>* Intravenous<br>Drug: ABBV-181<br>* Intravenous<br>* Other names: Budigalimab;|
| Experimental: Expansion Arm A: ABBV-927<br>Additional participants with HNSCC or NSCLC will receive intravenous (IV) doses of ABBV-927. | Drug: ABBV-927<br>* Intravenous<br>|
| Experimental: Expansion Arm B: ABBV-927+ABBV-181<br>Additional participants with HNSCC will receive IT doses of ABBV-927 and IV doses of ABBV-181. | Drug: ABBV-927<br>* Intratumoral<br>Drug: ABBV-181<br>* Intravenous<br>* Other names: Budigalimab;|
| Experimental: Expansion Arm C: ABBV-927+ABBV-181<br>Additional participants with NSCLC will receive IV doses of ABBV-927 and IV doses of ABBV-181. | Drug: ABBV-927<br>* Intravenous<br>Drug: ABBV-181<br>* Intravenous<br>* Other names: Budigalimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 | The MTD and the RPTD of ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 will be determined during the dose escalation phase of the study. Once the RPTD has been determined, the dose expansion portion will begin. | Up to 8 weeks | 
| Time to Cmax (Tmax) of ABBV-927 | Time to Cmax (Tmax) of ABBV-927. | Up to 12 weeks after participant's first dose | 
| Maximum observed serum concentration (Cmax) of ABBV-927 | Maximum observed serum concentration (Cmax) of ABBV-927. | Up to 12 weeks after participant's first dose | 
| Terminal-Phase Elimination Rate Constant (β) of ABBV-927 | Terminal-phase elimination rate constant (β)of ABBV-927. | Up to 12 weeks after participant's first dose | 
| Terminal half-life (t1/2) of ABBV-927 | Terminal half-life (t1/2) of ABBV-927. | Up to 4 weeks after participant's first dose | 
| Area under the serum concentration-time curve (AUCt) of ABBV-927 | Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-927. | Up to 12 weeks after participant's first dose | 
| Time to Cmax (Tmax) of ABBV-181 | Time to Cmax (Tmax) of ABBV-181. | Up to 12 weeks after participant's first dose | 
| Maximum observed serum concentration (Cmax) of ABBV-181 | Maximum observed serum concentration (Cmax) of ABBV-181. | Up to 12 weeks after participant's first dose | 
| Terminal-Phase Elimination Rate Constant (β) of ABBV-181 | Terminal-phase elimination rate constant (β)of ABBV-181. | Up to 12 weeks after participant's first dose | 
| Terminal half-life (t1/2) of ABBV-181 | Terminal half-life (t1/2) of ABBV-181. | Up to 4 weeks after participant's first dose | 
| Area under the serum concentration-time curve (AUCt) of ABBV-181 | Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-181. | Up to 12 weeks after participant's first dose | 
| Number of Participants with Adverse Events | An adverse event (AE) 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. | Up to 30 days after and up to 24-month of treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate (CBR, defined as the percentage of participants with a confirmed partial, complete response, or stable disease for at least 24 weeks to the treatment) | 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 and up to 24-month of treatment period | 
| Duration of objective response (DOR) | DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first. | Up to 30 days after and up to 24-month of treatment period | 
| Objective response rate (ORR) | ORR is defined as the proportion of participants with a confirmed partial or complete response to the treatment. | Up to 30 days after and up to 24-month of treatment period | 
| Progression-free survival (PFS) | PFS time is defined as the time from the first dose of ABBV-927 to disease progression or death, whichever occurs first. | Up to 30 days after and up to 24-month of treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer (NSCLC), Squamous cell carcinoma of the head and neck (SCCHN), Advanced solid tumor, Cancer, Pancreatic adenocarcinoma, Cutaneous melanoma, ABBV-927, ABBV-181, Budigalimab