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

AbbVie

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Drug: ABBV-368; Drug: ABBV-927; Drug: Nab-paclitaxel; Drug: ABBV-181; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03893955

M19-037

2019-000478-45 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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150 participants in 7 patient groups

Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors

Experimental group

Description:

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.

Treatment:

Drug: ABBV-927

Drug: ABBV-368

Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC

Experimental group

Description:

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.

Treatment:

Drug: ABBV-181

Drug: ABBV-927

Drug: ABBV-368

Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC

Experimental group

Description:

Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV.

Treatment:

Drug: Carboplatin

Drug: ABBV-927

Drug: ABBV-368

Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC

Experimental group

Description:

Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV.

Treatment:

Drug: Carboplatin

Drug: ABBV-181

Drug: ABBV-927

Dose Expansion Arm 3: ABBV-927 + Carboplatin TNBC

Experimental group

Description:

Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin by IV.

Treatment:

Drug: Carboplatin

Drug: ABBV-927

Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC

Experimental group

Description:

Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV.

Treatment:

Drug: Nab-paclitaxel

Drug: ABBV-927

Drug: ABBV-368

Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC

Experimental group

Description:

Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV.

Treatment:

Drug: ABBV-181

Drug: ABBV-927

Drug: ABBV-368