A Study With ABBV-155 Alone and in Combination With Taxane Therapy in Adults With Relapsed and/or Refractory Solid Tumors
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT03595059
- Lead Sponsor
- AbbVie
- Brief Summary
An open-label, dose-escalation (Part 1), dose-expansion (Part 2) study to assess the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-155 alone and in combination with paclitaxel or docetaxel.
In Part 1 (dose escalation), participants will receive escalating doses of ABBV-155 monotherapy (Part 1a) or ABBV-155 in combination with paclitaxel or docetaxel (Part 1b).
In Part 2 (dose expansion), participants will receive ABBV-155 monotherapy or in combination therapy. The ABBV-155 monotherapy cohort will enroll participants with relapsed or refractory (R/R) small cell lung cancer (SCLC) (Part 2a); the ABBV-155 plus a taxane (paclitaxel or docetaxel) combination cohort will enroll participants with R/R non-small cell lung cancer (NSCLC) and breast cancer (Part 2b).
- Detailed Description
The Escalation cohorts (Part 1) have been completed. The expansion cohorts (Part 2) are open to enrollment.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 169
-
Has a histologic or cytologic diagnosis of a malignant solid tumor.
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Participants enrolled in Part 2a (monotherapy, dose expansion) must have small cell lung cancer (SCLC) diagnosis; participants enrolled to Part 2b (combination therapy, dose expansion) must have either NSCLC or HR-positive/HER2-negative breast cancer.
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Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
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An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
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Failure of at least 1 prior systemic chemotherapy including all available standard therapies for participants in the dose-escalation phase (Parts 1a and 1b) including the safety lead-in phase (Japan only).
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All participants with breast cancer for subjects in the dose-expansion phase (Part 2b only) must have the following:
- Locally advanced or metastatic HR-positive/HER2-negative breast cancer after failing cyclin-dependent kinase (CDK)4/6 inhibitor-based therapy.
- HR-positivity and HER-2-negativity should be confirmed based on American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria.
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All participants with non-small cell lung cancer (NSCLC) for participants in the dose-expansion phase (Part 2b only) must have R/R NSCLC after at least 1 line of therapy. Participants with activating mutations in EGFR, ALK/ROS1, BRAF genes, or with positive expression of PD-L1 must have been treated with the appropriate targeted therapies.
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All participants with SCLC in the dose-expansion phase (Part 2a only) must have R/R SCLC from at least 1 line of therapy which includes a platinum-based therapy with or without an anti-PD-1/PD-L1 therapy.
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All participants with either breast cancer or NSCLC must have the following if exposed to prior taxane-based therapy:
- No history of taxane allergy (Part 1b and Part 2b only).
- Disease that has relapsed or progressed at least 2 months after most recent exposure to any taxane-based therapy.
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Available tumor tissue suitable for immunohistochemistry testing.
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Adequate kidney, liver, and hematologic laboratory values as described in the protocol.
- Untreated brain or meningeal metastases (participants with a history of metastases may be eligible based on details described in the protocol).
- Grade 2 or higher peripheral neuropathy (only applies to participants who would receive taxane therapy).
- Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
- Known active infection of hepatitis B, hepatitis C, or human immunodeficiency virus with exceptions as described in the protocol.
- Recent history (within 6 months) of congestive heart failure (defined in the protocol), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological or surgical intervention, pericardial effusion, or pericarditis.
- Any history of hypersensitivity to any ingredients of ABBV-155 will be excluded. For combination therapy only (Parts 1b and 2b), no history of serious allergic reaction to any taxane or any ingredients used in taxane formulation (e.g., cremaphor).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Expansion 2b: ABBV-155 + docetaxel in NSCLC Docetaxel Participants with non-small cell lung cancer (NSCLC) will be administered ABBV-155 (at or near the recommended Phase 2 dose identified for combination with paclitaxel in part 1b) in combination with docetaxel. Escalation 1a: ABBV-155 ABBV-155 Participants will be administered ABBV-155 (various doses). Expansion 2b: ABBV-155 + docetaxel in NSCLC ABBV-155 Participants with non-small cell lung cancer (NSCLC) will be administered ABBV-155 (at or near the recommended Phase 2 dose identified for combination with paclitaxel in part 1b) in combination with docetaxel. Escalation 1b: ABBV-155 + paclitaxel or docetaxel Paclitaxel Participants will be administered ABBV-155 (various doses) in combination with paclitaxel or docetaxel . Expansion 2a: ABBV-155 in SCLC ABBV-155 Description: Participants with small cell lung cancer (SCLC) will administer ABBV-155 (at the recommended Phase 2 dose). Escalation 1b: ABBV-155 + paclitaxel or docetaxel ABBV-155 Participants will be administered ABBV-155 (various doses) in combination with paclitaxel or docetaxel . Expansion 2b: ABBV-155 + paclitaxel in Breast Cancer ABBV-155 Participants with breast cancer will be administered ABBV-155 (at the recommended Phase 2 dose identified for combination with paclitaxel in part 1b) in combination with paclitaxel. Expansion 2b: ABBV-155 + paclitaxel in Breast Cancer Paclitaxel Participants with breast cancer will be administered ABBV-155 (at the recommended Phase 2 dose identified for combination with paclitaxel in part 1b) in combination with paclitaxel. Escalation 1b: ABBV-155 + paclitaxel or docetaxel Docetaxel Participants will be administered ABBV-155 (various doses) in combination with paclitaxel or docetaxel .
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to approximately 2 to 6 months ORR is defined as the percentage of participants with documented best response partial response (PR) or better according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
MTD and/or RPTD of ABBV-155 Up to approximately 21 days after initial dose of study drug The Maximum Tolerated Dose (MTD) and/or the Recommended Phase Two Dose (RPTD) of ABBV-155 will be determined during the dose escalation phase (Part 1).
- Secondary Outcome Measures
Name Time Method Tmax of ABBV-155 Up to approximately 48 days Time to maximum plasma concentration (Tmax).
Progression-Free Survival (PFS) Up to approximately 12 months PFS is defined as the number of days from the date of first dose of study drug to the date of the first documented PD or death due to any cause, whichever occurs first.
Number of Participants with Adverse Events (AE) Up to approximately 12 months An AE is defined as any untoward medical occurrence in a subject or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Duration of Response (DOR) Up to approximately 12 months DOR is defined as the number of days from the date of first documented response (PR or better) to the date of the first documented disease progression (PD) or death due to disease, whichever occurs first.
Rate of Complete Response (CR) Up to approximately 2 to 6 months CR is defined as the percentage of participants with documented best response CR according to RECIST version 1.1
Terminal Phase Elimination Rate constant of ABBV-155 Up to approximately 48 days Terminal phase elimination rate constant of ABBV-155
QTcF Change from Baseline Up to approximately 8 days QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level of ABBV-155 Monotherapy.
Cmax of ABBV-155 Up to approximately 48 days Maximum plasma concentration (Cmax).
Overall Survival (OS) Up to approximately 12 months after last dose of study drug OS is defined as the number of days from the date of first study drug to the date of death due to any cause.
AUCt of ABBV-155 Up to approximately 48 days Area under the plasma concentration versus time curve (AUC) from time 0 to the time of the last measurable concentration (AUCt).
AUCinf of ABBV-155 Up to approximately 48 days AUC from time 0 to infinite time (AUCinf).
t1/2 of ABBV-155 Up to approximately 48 days Terminal elimination half-life (t1/2).
Trial Locations
- Locations (40)
Mary Crowley Cancer Research /ID# 214168
🇺🇸Dallas, Texas, United States
Univ Hosp Cleveland /ID# 201567
🇺🇸Cleveland, Ohio, United States
Antoni van Leeuwenhoek /ID# 222260
🇳🇱Amsterdam, Noord-Holland, Netherlands
Universitair Medisch Centrum Utrecht /ID# 222357
🇳🇱Utrecht, Netherlands
The Chaim Sheba Medical Center /ID# 230812
🇮🇱Ramat Gan, Tel-Aviv, Israel
National Cancer Center Hospital East /ID# 215130
🇯🇵Kashiwa-shi, Chiba, Japan
National Cancer Center Hospital /ID# 215003
🇯🇵Chuo-ku, Tokyo, Japan
Maastricht Universitair Medisch Centrum /ID# 225220
🇳🇱Maastricht, Netherlands
National Taiwan University Hospital /ID# 205673
🇨🇳Taipei City, Taiwan
Rambam Health Care Campus /ID# 230813
🇮🇱Haifa, H_efa, Israel
Erasmus Medisch Centrum /ID# 222341
🇳🇱Rotterdam, Netherlands
China Medical University Hospital /ID# 214062
🇨🇳Taichung, Taiwan
Northwestern University Feinberg School of Medicine /ID# 201563
🇺🇸Chicago, Illinois, United States
Highlands Oncology Group, PA /ID# 201568
🇺🇸Springdale, Arkansas, United States
UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 206105
🇺🇸Orange, California, United States
Johns Hopkins Hospital /ID# 201320
🇺🇸Baltimore, Maryland, United States
Carolina BioOncology Institute /ID# 201577
🇺🇸Huntersville, North Carolina, United States
Duplicate_Cedars-Sinai Medical Center-West Hollywood /ID# 204267
🇺🇸West Hollywood, California, United States
Johns Hopkins Bayview Med Cnt /ID# 215095
🇺🇸Baltimore, Maryland, United States
Northwell Health - Marcus Ave /ID# 204376
🇺🇸New Hyde Park, New York, United States
Dana-Farber Cancer Institute /ID# 201564
🇺🇸Boston, Massachusetts, United States
Princess Margaret Cancer Centre /ID# 204539
🇨🇦Toronto, Ontario, Canada
Cross Cancer Institute /ID# 213838
🇨🇦Edmonton, Alberta, Canada
Peter MacCallum Cancer Center /ID# 241676
🇦🇺Melbourne, New South Wales, Australia
Pan American Center for Oncology Trials, LLC /ID# 232128
🇵🇷Rio Piedras, Puerto Rico
National Cancer Center /ID# 241095
🇰🇷Goyang-si, Gyeonggido, Korea, Republic of
Yonsei University Health System Severance Hospital /ID# 240648
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Hospital Universitario 12 de Octubre /ID# 239999
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz /ID# 239997
🇪🇸Madrid, Spain
National Cheng Kung University Hospital /ID# 206304
🇨🇳Tainan, Taiwan
Lifespan Cancer Institute at Rhode Island Hospital /ID# 204256
🇺🇸Providence, Rhode Island, United States
University of Alabama at Birmingham - Main /ID# 214024
🇺🇸Birmingham, Alabama, United States
Univ of Colorado Cancer Center /ID# 208365
🇺🇸Aurora, Colorado, United States
Yale University, Yale Cancer Center /ID# 201542
🇺🇸New Haven, Connecticut, United States
AdventHealth Cancer Institute - Orlando /ID# 227242
🇺🇸Orlando, Florida, United States
Henry Ford Hospital /ID# 226852
🇺🇸Detroit, Michigan, United States
University of Oklahoma, Stephenson Cancer Center /ID# 206820
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt Ingram Cancer Center /ID# 201575
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center /ID# 201558
🇺🇸Houston, Texas, United States
NEXT Oncology /ID# 204893
🇺🇸San Antonio, Texas, United States