A Phase I 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

Study Identifier:
M23-385
CT.gov Identifier:
NCT05599984
EudraCT Identifier:
202350000000
EU Trial (CTIS) Number:
2023-504598-18-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

To assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-706 as a monotherapy and in combination with budigalimab, carboplatin, or cisplatin in patients with advanced solid tumors. Safety endpoints include adverse events, clinical laboratory tests, vital signs, and dose-limiting toxicities. Biomarkers will also be evaluated. PK endpoints include Cmax, tmax, t1/2, and AUC. To evaluate ABBV-706 as monotherapy, or in combination with budigalimab, carboplatin, or cisplatin, in patients with advanced solid tumors expressing SEZ6, including small-cell lung cancer, NENs and high-grade Central Nervous System tumors

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part 1
    • Read More
  • Drug: Experimental: Part 2
  • Drug: Experimental: Part 3a
  • Drug: Experimental: Part 3b
  • Drug: Experimental: Part 4a
  • Drug: Experimental: Part 4b
  • Drug: Intervention/treatment:
  • Drug: Drug: Budigalimab
  • Drug: Drug: Cisplatin
  • Drug: Drug: Carboplatin
  • Drug: 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.
  • Drug: The study has 4 parts: (1) ABBV-706 monotherapy dose escalation in relapsed or refractory (R/R) solid tumors, following the Bayesian optimal interval (BOIN) design; (2) monotherapy dose optimization, randomized between two or more dose levels, and expansion in R/R SCLC; (3) dose escalation and expansion of ABBV-706 in combination with budigalimab or platinum therapy in R/R SCLC and NECs; (4) monotherapy dose expansion in R/R high-grade CNS tumors or NECs. ABBV-706 will be administered intravenously until disease progression, withdrawal of consent, or unacceptable toxicity.
  • Drug: The study has 4 parts: (1) ABBV-706 monotherapy dose escalation in relapsed or refractory (R/R) solid tumors with potential SEZ6 expression (Global cohort 1a; Japan cohort 1b), following a Bayesian optimal interval design; (2) monotherapy dose optimization, randomized between multiple dose levels (2a), and expansion (2b) in R/R SCLC; (3) dose escalation and expansion of ABBV-706 plus budigalimab (3a) or platinum therapy (3b) in R/R SCLC and NETs/ NECs; (4) monotherapy dose expansions in R/R high-grade CNS tumors (4a) and NETs/ NECs (4b).
  • Drug: Experimental Drugs
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • 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: Participants with R/R SCLC following at least 1 prior platinum-containing chemotherapy or R/R poorly differentiated NECs, e.g., NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant Non-small cell lung cancer (NSCLC), atypical lung carcinoids, other high-grade poorly differentiated NECs.
    • Part 3b only: Participants with R/R SCLC who have only progressed following a frontline regimen containing a platinum-based chemotherapy or R/R NECs, e.g., NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, other NECs.
    • Part 4a only: Participants with R/R 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) who have progressed on SoC therapy and with no curative therapy options available.
    • Part 4b only: Participants with R/R neuroendocrine tumors, including NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, and other high-grade poorly differentiated NECs, who have progressed on SoC therapy and with no curative therapy options available.
    • 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.
    • Trial eligibility: patients ≥18 years of age with R/R SCLC, NETs/ NECs, or high-grade CNS tumors and measurable disease per RECIST v1.1 or RANO, with an ECOG score ≤1. Tumor tissue for retrospective SEZ6 expression analysis is required
    Exclusion criteria
    • 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.
    • Prior exposure to SEZ6-targeted ADCs or ADCs with Top1i payload was not permitted.

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Kyriakos Papadopoulos
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Location
    START Barcelona
    Barcelona, Spain, 08023
    Investigator
    Tatiana Hernandez Guerrero
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Sreenivasa Chandana
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Emiliano Calvo
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Solid Tumor