A Study of Adverse Events, How Intravenously (IV) Infused ABBV-303 Moves Through the Body, and Change in Disease State, as Monotherapy and in Combination With IV Infused Budigalimab (ABBV-181), in Adult Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-303 as a monotherapy and in combination with budigalimab, (ABBV-181). ABBV-303 is an investigational drug being developed for the treatment of solid tumors. There are multiple treatment arms in this study. Participants will either receive ABBV-303 as a single agent or in combination with budigalimab (another investigational drug) at different doses. Approximately 181 adult participants will be enrolled in the study across sites worldwide. In Part A, ABBV-303 will be intravenously (IV) infused in escalating doses as a monotherapy in participants with relapsed (R)/refractory (R) solid tumors, R/R non-small cell lung cancer (NSCLC), R/R renal cell carcinoma (RCC), R/R head and neck squamous cell carcinoma (HNSCC), or R/R tissue agnostic participants with mesenchymal epithelial transition. In Part B, ABBV-303 in combination with budigalimab will be IV infused in participants with R/R solid tumors or NSCLC. The estimated duration of the study is up to 3 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.

Official Title
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A Phase 1 First-in-Human, Open-Label Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABBV-303, as Monotherapy and in Combination With Budigalimab (ABBV-181), in Adult Subjects With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: ABBV-303
* Drug: Budigalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Laboratory values meeting the protocol's criteria within the screening period (-28 days) prior to the first dose of study drug. Participants with a diagnosis of a malignant solid tumor by histology (World Health Organization [WHO] criteria). Participants with measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Exclusion Criteria: Unresolved Grade > 1 AEs from prior anti-cancer therapy except for alopecia. Active systemic or uncontrolled local bacterial, fungal, or viral infection requiring antimicrobial therapy. History of hypersensitivity to the active ingredients or any excipients of ABBV-303 and budigalimab (ABBV-181). Body weight < 35 kg.

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-303 Dose Escalation: Part 1A Monotherapy<br>Participants with (R)/refractory (R) solid tumors will receive ABBV-303 in escalating doses as a monotherapy until the maximum tolerable dose (MTD) is determined as part of the 3 year study duration. | Drug: ABBV-303<br>* Intravenous (IV) Infusion<br>|
| Experimental: ABBV-303 Dose Expansion: Part 2A Monotherapy<br>Participants with R/R NSCLC will receive ABBV-303 at the recommended phase 1 expansion dose (RP1ED) as a monotherapy as part of the 3 year study duration. | Drug: ABBV-303<br>* Intravenous (IV) Infusion<br>|
| Experimental: ABBV-303 Dose Expansion: Part 3A Monotherapy<br>Participants with R/R RCC will receive ABBV-303 at the RP1ED as a monotherapy as part of the 3 year study duration. | Drug: ABBV-303<br>* Intravenous (IV) Infusion<br>|
| Experimental: ABBV-303 Dose Expansion: Part 4A Monotherapy<br>Participants with R/R HNSCC will receive ABBV-303 at the RP1ED as a monotherapy as part of the 3 year study duration. | Drug: ABBV-303<br>* Intravenous (IV) Infusion<br>|
| Experimental: ABBV-303 Dose Expansion: Part 5A Monotherapy<br>Tissue agnostic with R/R participants with MET amplification by any commercially available test will receive ABBV-303 at the RP1ED as a monotherapy as part of the 3 year study duration. | Drug: ABBV-303<br>* Intravenous (IV) Infusion<br>|
| Experimental: ABBV-303 Dose Escalation: Part 1B Combination<br>Participants with R/R solid tumors will receive ABBV-303 in combination with budigalimab at or below the MTD as part of the 3 year study duration. | Drug: ABBV-303<br>* Intravenous (IV) Infusion<br>Drug: Budigalimab<br>* IV Infusion<br>* Other names: ABBV-181;|
| Experimental: ABBV-303 Dose Expansion: Part 2B Combination<br>Participants with R/R NSCLC will receive ABBV-303 at or below the MTD in combination with budigalimab as part of the 3 year study duration. | Drug: ABBV-303<br>* Intravenous (IV) Infusion<br>Drug: Budigalimab<br>* IV Infusion<br>* Other names: ABBV-181;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AE) | An AE is 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 3 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | ORR defined as percentage of participants with confirmed best overall response of Confirmed complete response (CR) and partial response (PR) per investigator review according to RECIST version 1.1. | Up to 3 Years | 
| Duration of Response (DOR) for Participants with Confirmed CR/PR per RECIST v1.1 | DOR is defined for participants achieving a confirmed CR+PR as the time from the initial response of CR+PR per investigator review according to RECIST 1.1 criteria to disease progression or death of any cause, whichever occurs earlier. | Up to 3 Years | 
| Progression-free survival (PFS) | PFS is defined as time from first study treatment to a documented disease progression according to RECIST version 1.1, as determined by the investigator, or death due to any cause, whichever occurs earlier. | Up to 3 Years | 
| Overall survival (OS) | OS is defined as time from first study treatment to death due to any cause. | Up to 3 Years | 
| ORR per Immune-Mediated Response Evaluation Criteria in Solid Tumors (iRECIST) | ORR defined as percentage of participants with confirmed best overall response of Confirmed complete response (CR) and partial response (PR) per investigator review according to iRECIST version 1.1. | Up to 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, Non-Small Cell Lung Cancer, NSCLC, Renal Cell Carcinoma, RCC, Head and Neck Squamous Cell Carcinoma, HNSCC, ABBV-303, ABBV-181, Budigalimab