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
- Conditions
- Advanced Solid TumorsCancerTriple-Negative Breast Cancer (TNBC)Non-small-cell-lung-cancer (NSCLC)Metastatic Solid Tumors
- Interventions
- Registration Number
- NCT03893955
- Lead Sponsor
- AbbVie
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 150
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC ABBV-368 Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV. Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors ABBV-927 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. Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC ABBV-927 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. Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC ABBV-181 Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV. Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC ABBV-927 Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV. Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors ABBV-368 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. Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC ABBV-368 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. Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC ABBV-927 Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV. Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC ABBV-927 Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV. Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC Nab-paclitaxel Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV. Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC ABBV-181 Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV. Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC ABBV-368 Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV. Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC ABBV-181 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. Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC ABBV-927 Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV. Dose Expansion Arm 3: ABBV-927 + Carboplatin TNBC ABBV-927 Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin by IV. Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC ABBV-368 Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV. Dose Expansion Arm 3: ABBV-927 + Carboplatin TNBC Carboplatin Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin by IV. Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC Carboplatin Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV. Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC Carboplatin Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV.
- Primary Outcome Measures
Name Time Method Dose Expansion: Objective Response Rate (ORR) Up to approximately 2 years following the first dose of study drug 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.
Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 Up to approximately 6 months 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.
Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181 Up to approximately 6 months 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.
- Secondary Outcome Measures
Name Time Method Maximum Serum Concentration (Cmax) Up to approximately 12 weeks after participant's initial dose of study drug Maximum Serum Concentration (Cmax)
Dose-Expansion Phase: Progression-free Survival (PFS) Up to approximately 2 years since the first dose of study drug PFS is defined as the time from date of first study drug exposure to disease progression or death, whichever occurs first.
Time to Maximum Observed Serum Concentration (Tmax) Up to approximately 12 weeks after participant's initial dose of study drug Time to Maximum Observed Serum Concentration (Tmax)
Terminal Phase Elimination Half-life (t1/2) Up to approximately 4 weeks after participant's initial dose of study drug Terminal Phase Elimination Half-life (t1/2)
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 Area under the serum concentration versus time curve from time 0 to the time of the last measurable concentration (AUCτ).
Dose-Expansion Phase: Duration of Response (DOR) Up to approximately 2 years since the first dose of study drug DOR defined as the time from the participant's initial response to study drug therapy to disease progression or death, whichever occurs first.
Trial Locations
- Locations (26)
Hospital Universitario Fundacion Jimenez Diaz /ID# 212806
🇪🇸Madrid, Spain
Icon Cancer Centre /ID# 224084
🇦🇺South Brisbane, Queensland, Australia
Fort Wayne Medical Oncology and Hematology, Inc /ID# 226072
🇺🇸Fort Wayne, Indiana, United States
Hospital Universitario Virgen de la Victoria /ID# 221671
🇪🇸Malaga, Spain
UPMC Hillman Cancer Ctr /ID# 222747
🇺🇸Pittsburgh, Pennsylvania, United States
St Jude Hospital dba St Joseph /ID# 211130
🇺🇸Santa Rosa, California, United States
Hospital Universitario Vall d'Hebron /ID# 212804
🇪🇸Barcelona, Spain
Virginia Cancer Specialists - Fairfax /ID# 210671
🇺🇸Fairfax, Virginia, United States
Duke Cancer Center /ID# 217641
🇺🇸Durham, North Carolina, United States
NEXT Oncology /ID# 210717
🇺🇸San Antonio, Texas, United States
Tennessee Oncology-Nashville Centennial /ID# 221400
🇺🇸Nashville, Tennessee, United States
Highlands Oncology Group, PA /ID# 218863
🇺🇸Springdale, Arkansas, United States
Institut Curie /ID# 223475
🇫🇷Paris CEDEX 05, Paris, France
National Taiwan University Hospital /ID# 210993
🇨🇳Taipei City, Taipei, Taiwan
The Chaim Sheba Medical Center /ID# 211699
🇮🇱Ramat Gan, Tel-Aviv, Israel
China Medical University Hospital /ID# 221090
🇨🇳Taichung, Taiwan
Carolina BioOncology Institute /ID# 210664
🇺🇸Huntersville, North Carolina, United States
Washington University-School of Medicine /ID# 221399
🇺🇸Saint Louis, Missouri, United States
Mary Crowley Cancer Research /ID# 210716
🇺🇸Dallas, Texas, United States
Centre Leon Berard /ID# 217910
🇫🇷Lyon CEDEX 08, Rhone, France
Institut de Cancérologie de l'Ouest René Gauducheau /ID# 212880
🇫🇷St Herblain CEDEX, Loire-Atlantique, France
Centre Jean Perrin /ID# 217911
🇫🇷Clermont Ferrand, France
AP-HP - Hopital Bichat - Claude-Bernard /ID# 212869
🇫🇷Paris, France
Hospital Universitario HM Sanchinarro /ID# 212805
🇪🇸Madrid, Spain
Yale University School of Medicine /ID# 210678
🇺🇸New Haven, Connecticut, United States
Moffitt Cancer Center /ID# 215037
🇺🇸Tampa, Florida, United States