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-706 as a monotherapy and in combination with budigalimab, carboplatin, or cisplatin. ABBV-706 is an investigational drug being developed for the treatment of small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors and high-grade neuroendocrine carcinomas (NECs). There are multiple treatment arms in this study. Participants will either receive ABBV-706 as a single agent or in combination with budigalimab (another investigational drug), carboplatin or cisplatin at different doses. Approximately 319 adult participants will be enrolled in the study across sites worldwide. In part 1 (dose escalation), ABBV-706 will be intravenously infused in escalating doses as a monotherapy until the maximum tolerated dose (MTD) is determined in participants with SCLC, high-grade CNS tumors, and high-grade NECs. In part 2, multiple doses will be selected from Part 1 and SCLC participants will be assigned to one of these doses in a randomized fashion to determine the recommended Phase 2 dose. In Part 3a, participants with SCLC or NECs will receive ABBV-706 in combination with budigalimab intravenously every 3 weeks. In Part 3b participants with SCLC or NECs will receive ABBV-706 in combination with either carboplatin or cisplatin intravenously. In Part 4a, participants with CNS tumors will receive ABBV-706 intravenously at a dose determined from Part 1. In Part 4b, participants with NECs will receive ABBV-706 intravenously at a dose selected from Part 1. The estimated duration of the study is up to 4 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
288
Intravenous (IV) Infusion
Intravenous infusion
IV Infusion
Intravenous infusion
Banner MD Anderson Cancer Ctr /ID# 260129
Gilbert, Arizona, United States
City Of Hope Comprehensive Cancer Center /ID# 271295
Duarte, California, United States
City of Hope - Orange County Lennar Foundation Cancer Center /ID# 259884
Irvine, California, United States
Yale New Haven Hospital /ID# 246647
New Haven, Connecticut, United States
Georgetown University Hospital /ID# 255352
Washington D.C., District of Columbia, United States
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.
Time frame: Up to Approximately 2 Years
Maximum Observed Serum/Plasma Concentration (Cmax) of ABBV-706
Maximum observed serum/plasma concentration of ABBV-706.
Time frame: Up to Approximately 2 Years
Time to Cmax (Tmax) of ABBV-706
Time to Cmax of ABBV-706.
Time frame: Up to Approximately 2 Years
Terminal Phase Elimination Half-Life (t1/2) of ABBV-706
Terminal phase elimination half-life (t1/2) of ABBV-706.
Time frame: Up to Approximately 2 Years
Area Under the Serum/Plasma Concentration-Time Curve (AUC) of ABBV-706
Area under the serum/plasma concentration-time curve of ABBV-706.
Time frame: Up to Approximately 2 Years
Antidrug Antibodies (ADAs)
Incidence and concentration of anti-drug antibodies.
Time frame: Up to Approximately 2 Years
Neutralizing Antibodies (nAbs)
Incidence and concentration of neutralizing antibodies.
Time frame: Up to Approximately 2 Years
Percentage of Participants with Objective Response, for Participants with Extracranial Solid Tumors
Objective response is defined as participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 for for extracranial solid tumors per investigator assessment.
Time frame: Up to Approximately 2 Years
Recommended Phase 2 Dose (RP2D) of ABBV-706
The RP2D will be determined using all available information, including, but not limited to, AEs, dose-limiting toxicities, pharmacokinetic parameters, clinical laboratory tests, and efficacy measures.
Time frame: Up to Approximately 2 Years
Percentage of Participants with Objective Response for Participants with Central Nervous System (CNS) Tumors
Objective response is as participants achieving a confirmed best overall response of CR and PR according to Response Assessment for Neuro-Oncology (RANO), version 1.1 for CNS tumors per investigator assessment.
Time frame: Up to Approximately 2 Years
Duration of response (DOR) for Participants with Confirmed CR/PR
For participants achieving a confirmed CR/PR, DOR is defined as the time from the initial response of CR/PR to disease progression or death of any cause, whichever occurs earlier.
Time frame: Up to Approximately 2 Years
Percentage of Participants with Clinical Benefit
Clinical benefit is defined as a participant achieving CR/PR, or Stable Disease (SD).
Time frame: Up to Approximately 2 Years
Progression-Free Survival (PFS)
PFS is defined as time from first study treatment to a documented disease progression, as determined by the investigator, or death due to any cause, whichever occurs earlier.
Time frame: Up to Approximately 2 Years
Overall survival (OS)
OS is defined as time from first study treatment to death due to any cause.
Time frame: Up to Approximately 2 Years
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University of Chicago Medical Center /ID# 256334
Chicago, Illinois, United States
Fort Wayne Medical Oncology and Hematology, Inc /ID# 260130
Fort Wayne, Indiana, United States
University of Iowa Hospitals and Clinics /ID# 246638
Iowa City, Iowa, United States
Barbara Ann Karmanos Cancer In /ID# 261799
Detroit, Michigan, United States
Henry Ford Hospital /ID# 246648
Detroit, Michigan, United States
...and 56 more locations