A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-927 With ABBV-368, Budigalimab (ABBV-181) and/or Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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A study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-927 with ABBV-368, Budigalimab (ABBV-181) and/or chemotherapy in participants with selected solid tumors. This study consists of 2 main parts, a dose-escalation phase and a dose-expansion phase. The dose-expansion phase can begin once the recommended phase 2 dose/maximum tolerated dose (RP2D/MTD) is determined in the dose-escalation phase.

Official Title
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A Phase 1, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Combinations of ABBV-927 With ABBV-368, Budigalimab (ABBV-181) and/or Chemotherapy in Subjects With Locally Advanced or Metastatic Solid Tumors

Conditions
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Cancer, Advanced Solid Tumors, Triple-Negative Breast Cancer (TNBC), Non-small-cell-lung-cancer (NSCLC), Metastatic Solid Tumors

Intervention / Treatment
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* Drug: ABBV-927
* Drug: ABBV-368
* Drug: ABBV-181
* Drug: Carboplatin
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adequate liver, kidney and hematology function as demonstrated by laboratory values detailed in the study protocol. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Dose-Escalation: Arm A: Participants with an advanced solid tumor who have progressed on standard therapies known to provide clinical benefit and/or participants who have refused or are intolerant of such therapy. Arm B (non-small-cell-lung-cancer [NSCLC]): Participants with histologically or cytologically confirmed NSCLC who previously progressed during or after an anti-programmed cell death (PD)-1 or PD ligand 1 (PD-L1) therapy and a platinum-based regimen in the recurrent or metastatic setting. Dose-Expansion: Arm 1, 2, and 3 (triple-negative breast cancer [TNBC]): Participants with histologically or cytologically confirmed breast adenocarcinoma that is estrogen receptor/progesterone receptor/human epidermal growth factor receptor (HER)2-negative who must have disease progression during or after at least 1 systemic therapy that included a taxane in the metastatic or recurrent setting and who are treatment-naïve to immunotherapy. Arm 4 (TNBC): Participants with histologically or cytologically confirmed TNBC who have received no previous anti-cancer therapy for TNBC, and who are PD-L1 negative on tumor tissue by immunohistochemistry (IHC) assay. Arm 5 (NSCLC): Participants with histologically or cytologically confirmed NSCLC who previously progressed either during or after an anti-PD-1 or PD-L1 therapy and a platinum-based regimen in the recurrent or metastatic setting. Exclusion Criteria: Has history of inflammatory bowel disease or pneumonitis. Has uncontrolled metastases to the central nervous system. Has a concurrent malignancy that is clinically significant, treatment is required, or the participant is not clinically stable. Has had a major surgery ≤ 28 days prior to the first dose of study drug or the surgical wound is not fully healed. Has previously treated with an anti-PD- or PD-L1-targeting agent and had during the course of their therapy: any immune-mediated toxicity of Grade 3 or worse severity treatment of the toxicity with systemic corticosteroids any hypersensitivity to the PD-1 or PD-L1-targeting agent any treatment-related toxicity resulting in discontinuation of the PD-1 or PD-L1 targeting agent

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: Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors<br>Participants with Solid Tumors will receive various doses of ABBV-927 by intravenous (IV) infusion plus ABBV-368. This will determine the recommended phase two dose (RP2D) of ABBV-927. | Drug: ABBV-927<br>* Intravenous (IV) Infusion<br>Drug: ABBV-368<br>* Intravenous (IV) Infusion<br>|
| Experimental: Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC<br>Participants with non-small-cell-lung-cancer (NSCLC) will receive ABBV-927 IV at various dose levels + ABBV-368 + ABBV-181. This will determine the recommended phase two dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181. | Drug: ABBV-927<br>* Intravenous (IV) Infusion<br>Drug: ABBV-368<br>* Intravenous (IV) Infusion<br>Drug: ABBV-181<br>* Intravenous (IV) Infusion<br>* Other names: Budigalimab;|
| Experimental: Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC<br>Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV. | Drug: ABBV-927<br>* Intravenous (IV) Infusion<br>Drug: ABBV-368<br>* Intravenous (IV) Infusion<br>Drug: Carboplatin<br>* Intravenous (IV) Infusion<br>|
| Experimental: Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC<br>Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV. | Drug: ABBV-927<br>* Intravenous (IV) Infusion<br>Drug: ABBV-181<br>* Intravenous (IV) Infusion<br>* Other names: Budigalimab;Drug: Carboplatin<br>* Intravenous (IV) Infusion<br>|
| Experimental: Dose Expansion Arm 3: ABBV-927 + Carboplatin TNBC<br>Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin by IV. | Drug: ABBV-927<br>* Intravenous (IV) Infusion<br>Drug: Carboplatin<br>* Intravenous (IV) Infusion<br>|
| Experimental: Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC<br>Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV. | Drug: ABBV-927<br>* Intravenous (IV) Infusion<br>Drug: ABBV-368<br>* Intravenous (IV) Infusion<br>Drug: Nab-paclitaxel<br>* Intravenous (IV) Infusion<br>|
| Experimental: Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC<br>Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV. | Drug: ABBV-927<br>* Intravenous (IV) Infusion<br>Drug: ABBV-368<br>* Intravenous (IV) Infusion<br>Drug: ABBV-181<br>* Intravenous (IV) Infusion<br>* Other names: Budigalimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Expansion: Objective Response Rate (ORR) | ORR is defined as the percentage of participants with either complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Up to approximately 2 years following the first dose of study drug | 
| Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 | The RP2D of ABBV-927 + ABBV-368 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics data. | Up to approximately 6 months | 
| Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181 | The RP2D of ABBV-927 + ABBV-368 + ABBV-181 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics data. | Up to approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Expansion Phase: Progression-free Survival (PFS) | PFS is defined as the time from date of first study drug exposure to disease progression or death, whichever occurs first. | Up to approximately 2 years since the first dose of study drug | 
| Dose-Expansion Phase: Duration of Response (DOR) | DOR defined as the time from the participant's initial response to study drug therapy to disease progression or death, whichever occurs first. | Up to approximately 2 years since the first dose of study drug | 
| Maximum Serum Concentration (Cmax) | Maximum Serum Concentration (Cmax) | Up to approximately 12 weeks after participant's initial dose of study drug | 
| Time to Maximum Observed Serum Concentration (Tmax) | Time to Maximum Observed Serum Concentration (Tmax) | Up to approximately 12 weeks after participant's initial dose of study drug | 
| Area Under the Serum Concentration Versus Time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCτ) | Area under the serum concentration versus time curve from time 0 to the time of the last measurable concentration (AUCτ). | Up to approximately 12 weeks after participant's initial dose of study drug | 
| Terminal Phase Elimination Half-life (t1/2) | Terminal Phase Elimination Half-life (t1/2) | Up to approximately 4 weeks after participant's initial dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Advanced Solid Tumors, Triple-Negative Breast Cancer (TNBC), Non-small-cell-lung-cancer (NSCLC), ABBV-927, ABBV-368, ABBV-181, metastatic solid tumors, dose-escalation, recommended phase 2 dose, budigalimab