Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors

NCT05599984
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Phase
Phase 1
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Recruitment status
Active, not recruiting
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Participants
288
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Lead sponsor
AbbVie
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Start date
2022-12-05
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Number of sites
66
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Summary
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.
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Short title
Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors
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Official title
A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-706 as Monotherapy and in Combination With Budigalimab (ABBV-181), Carboplatin, or Cisplatin in Adult Subjects With Advanced Solid Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-11-01
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First posted
2022-10-31
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Registry last updated
2026-05-07
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Primary completion date
2027-11-01
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Start date
2022-12-05
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Actual participants
288
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Participants
288
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
66
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
AbbVie
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05599984
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ClinicalTrials.gov ID
NCT05599984
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Percentage of Participants With Adverse Events (AE)

    Timeframe: Up to Approximately 2 Years

    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.

  2. Maximum Observed Serum/Plasma Concentration (Cmax) of ABBV-706

    Timeframe: Up to Approximately 2 Years

    Maximum observed serum/plasma concentration of ABBV-706.

  3. Time to Cmax (Tmax) of ABBV-706

    Timeframe: Up to Approximately 2 Years

    Time to Cmax of ABBV-706.

  4. Terminal Phase Elimination Half-Life (t1/2) of ABBV-706

    Timeframe: Up to Approximately 2 Years

    Terminal phase elimination half-life (t1/2) of ABBV-706.

  5. Area Under the Serum/Plasma Concentration-Time Curve (AUC) of ABBV-706

    Timeframe: Up to Approximately 2 Years

    Area under the serum/plasma concentration-time curve of ABBV-706.

  6. Antidrug Antibodies (ADAs)

    Timeframe: Up to Approximately 2 Years

    Incidence and concentration of anti-drug antibodies.

  7. Neutralizing Antibodies (nAbs)

    Timeframe: Up to Approximately 2 Years

    Incidence and concentration of neutralizing antibodies.

  8. Percentage of Participants with Objective Response, for Participants with Extracranial Solid Tumors

    Timeframe: Up to Approximately 2 Years

    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.

  9. Recommended Phase 2 Dose (RP2D) of ABBV-706

    Timeframe: Up to Approximately 2 Years

    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.

  10. Percentage of Participants with Objective Response for Participants with Central Nervous System (CNS) Tumors

    Timeframe: Up to Approximately 2 Years

    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.

  11. Duration of response (DOR) for Participants with Confirmed CR/PR

    Timeframe: Up to Approximately 2 Years

    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.

  12. Percentage of Participants with Clinical Benefit

    Timeframe: Up to Approximately 2 Years

    Clinical benefit is defined as a participant achieving CR/PR, or Stable Disease (SD).

  13. Progression-Free Survival (PFS)

    Timeframe: Up to Approximately 2 Years

    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.

  14. Overall survival (OS)

    Timeframe: Up to Approximately 2 Years

    OS is defined as time from first study treatment to death due to any cause.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • The laboratory values criteria must be met within 7 days prior to the first dose of study drug as per the protocol.
  • QT interval corrected for heart rate (QTc) <= 450 msec (males) or <= 470 msec (females) using Fridericia's correction, and an ejection fraction of >= 50% as measured by echocardiogram or multigated acquisition (MUGA) scan at Screening.
  • Part 1 only: Advanced recurrent or refractory solid tumors with potential SEZ6 expression including small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors (glioblastoma [GBM], IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4), neuroendocrine prostate cancer (NEPC), high-grade poorly differentiated gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)s, large cell neuroendocrine carcinoma (LCNEC)s, SCLC transformed from epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), atypical lung carcinoids, and other high-grade poorly differentiated NECs, who have progressed on or after standard of care (SoC) therapy and with no curative therapy available. For SCLC, participants must have histologically or cytologically confirmed SCLC that is relapsed or refractory following at least 1 prior platinum-containing chemotherapy.
  • Part 2 only: Histologically or cytologically confirmed SCLC that is relapsed or refractory (R/R) following at least 1 prior platinum-containing chemotherapy and with no curative therapy available. For the purposes of this study, a line of therapy is defined as >= 1 complete cycle of either a single agent or combination of drugs, including any planned sequential therapy of various regimens.
  • Part 3a only: SCLC or Grade 3 NETs and poorly differentiated NECs. Specific tumor types include but not limited to NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, MTC, and other NECs (atypical lung carcinoids that have received prior chemotherapy are allowed)
  • Part 3b only: SCLC who have only progressed following a frontline regimen containing a platinum-based chemotherapy (i.e., second-line SCLC subjects) or Grade 3 NETs and poorly differentiated NECs. Specific tumor types include but not limited to NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, MTC, and other NECs (atypical lung carcinoids that have received prior chemotherapy are allowed)tumors (GBM, IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4) who have progressed on SoC therapy and with no curative therapy options available.
  • Part 4b only: Grade 3 NETs and poorly differentiated NECs. Specific tumor types include but not limited to NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, MTC, and other NECs (atypical lung carcinoids that have received prior chemotherapy are allowed)
  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for participants with extracranial solid tumors or Response Assessment for Neuro-Oncology (RANO)for participants with primary high-grade CNS tumors (GBM, IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4).
  • Primary CNS tumors within 12 weeks from radiation therapy should have unequivocal progression as documented by either tumor recurrence predominantly outside of radiation field on magnetic resonance imaging (MRI) or confirmed on tumor biopsy.
  • Participants with brain metastases from an extracranial solid tumor are eligible if the brain metastases as outlined in the protocol.
  • Fresh or archival tumor tissue available for submission, for retrospective SEZ6 expression analysis as outlined in the protocol.

  • History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or pneumonitis.
  • History of idiopathic pulmonary fibrosis or organizing pneumonia.
  • Prior treatment with an antibody drug conjugate that consists of a Top1 inhibitor payload.
  • Part 2 only: Prior treatment with a SEZ6-targeted antibody drug conjugate.
Sources for eligibility
clinicaltrials.gov

  • Banner MD Anderson Cancer Ctr /ID# 260129Gilbert, United States
  • City Of Hope Comprehensive Cancer Center /ID# 271295Duarte, United States
  • City of Hope - Orange County Lennar Foundation Cancer Center /ID# 259884Irvine, United States
  • Yale New Haven Hospital /ID# 246647New Haven, United States
  • Georgetown University Hospital /ID# 255352Washington D.C., United States
  • University of Chicago Medical Center /ID# 256334Chicago, United States
  • Fort Wayne Medical Oncology and Hematology, Inc /ID# 260130Fort Wayne, United States
  • University of Iowa Hospitals and Clinics /ID# 246638Iowa City, United States
  • Barbara Ann Karmanos Cancer In /ID# 261799Detroit, United States
  • Henry Ford Hospital /ID# 246648Detroit, United States
  • START Midwest /ID# 251257Grand Rapids, United States
  • St. Lukes Hosp. of Kansas City /ID# 259958Kansas City, United States
  • Washington University-School of Medicine /ID# 246286St Louis, United States
  • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 246303New York, United States
  • Duke Cancer Center /ID# 246285Durham, United States
  • UH Cleveland Medical Center /ID# 246641Cleveland, United States
  • Univ Oklahoma HSC /ID# 250884Oklahoma City, United States
  • Tennessee Oncology, PLLC /ID# 246283Nashville, United States
  • University of Texas MD Anderson Cancer Center /ID# 246287Houston, United States
  • South Texas Accelerated Research Therapeutics /ID# 248946San Antonio, United States
  • University of Utah /ID# 246640Salt Lake City, United States
  • Northwest Medical Specialties - Tacoma /ID# 262801Tacoma, United States
  • Chris O'Brien Lifehouse /ID# 259087Camperdown, Australia
  • The Kinghorn Cancer Centre /ID# 260874Darlinghurst, Australia
  • Austin Health and Ludwig Institute for Cancer Research /ID# 255174Heidelberg, Australia

And 41 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-504598-18-00
Sources for references
clinicaltrials.gov

Related records

Drugs (3)

Lead sponsors (1)

Conditions (3)

Targets (1)