A Phase I First in Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-400 as Monotherapy and in Combination With Bevacizumab in Adult Subjects With Advanced Solid Tumors

Study Identifier:
M21-404
CT.gov Identifier:
NCT05029882
EudraCT Identifier:
2021-002258-98
EU Trial (CTIS) Number:
2023-509335-60-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

To assess adverse events and change in disease activity when ABBV-400 is given to adult participants to treat advanced solid tumors.

Dose escalation phase- to determine the best dose of ABBV-400

Dose expansion phase- to confirm the dose.

To evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of ABBV-400 monotherapy in patients with

advanced solid tumors and determine the recommended phase 2 dose

To evaluate safety, tolerability, and pharmacokinetics (PK) of ABBV-400 in patients (pts) with advanced solid tumors; determine the recommended phase 2 dose; and assess preliminary efficacy in NSCLC and GEA expressing c-Met.

DLTs will be assessed during the first cycle.

Safety will be evaluated by AE monitoring, vital sign measurements, physical exam, and clinical lab testing.

PK endpoints include maximum observed serum concentration and area under the curve.

Intensive PK samples are being collected on cycles 1 and 3; antidrug antibody (ADA) samples are being collected at regular intervals. PK were characterized for 3 analytes, ABBV-400 conjugate, total antibody, and free payload across the range of doses evaluated in the dose escalation phase. PK analyses were performed using non-compartmental analysis and ADA data was summarized.

To assess pharmacokinetic (PK) and immunogenicity

Population pharmacokinetics (PK) and exposure-response (E-R) analyses were conducted to characterize ABBV-400 conjugate and unconjugated payload PK and the relationship between exposures and efficacy (objective response rate [ORR]) and safety (Grade (Gr) ≥ 3 neutropenia, anemia and thrombocytopenia) endpoints. Relative dose intensity (RDI) analysis was performed.

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.
  • Non-Small Cell Lung Cancer
  • Solid Tumor
  • Gastroesophageal
  • Bowel (Colorectal)
    • 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 (Monotherapy Dose Escalation)
    • Read More
  • Drug: Experimental: Part 2i (wtEGFR Non-Small Cell Lung Cancer [NSCLC])
  • Drug: Experimental: Part 2ii (mutEGFR NSCLC)
  • Drug: Experimental: Part 2iii (Squamous NSCLC)
  • Drug: Experimental: Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct
  • Drug: Experimental: Part 4 (Colorectal Cancer)
  • Drug: Experimental: Part 5 (MET Amplification)
  • Drug: Experimental: Part 6 (MET Mutation)
  • Drug: Experimental: Part 7a (Combination Dose Escalation)
  • Drug: Drug: Bevacizumab
  • Drug: Experimental: Part 7bi (Combination Dose Optimization Low Dose)
  • Drug: Experimental: Part 7bii (Combination Dose Optimization High Dose)
  • Drug: Experimental: Part 7biii (Combination Comparator)
  • Drug: Patients received 2.4 and 3.0 mg/kg doses administered once every 3 weeks
  • Drug: ASCO 2024
  • Drug: ESMO 2024:
  • Drug: ASCO 2025:
  • Drug: Unselected pts with advanced CRC were enrolled in 2 parts: (1) Safety lead-in: pts received escalating doses of Temab-A at 1.6 (n=7) or 2.4 (n=8) mg/kg (2.0 mg/kg backfill [n=5]) + Bev 7.5 mg/kg Q3W; (2) Dose optimization: pts were randomized to Temab-A 2.0 (n=23) or 2.4 (n=22) mg/kg + Bev 7.5 mg/kg Q3W, or trifluridine/tipiracil (TAS-102) 35 mg/m2 days 1-5 and 8-12 Q4W + Bev 5.0 mg/kg (n=21) Q2W (SOC)
  • Drug: Pts received Temab-A at 1.6, 2.0 (backfill), 2.4, and 3.0 mg/kg Q3W.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Diagnosis of malignant solid tumor (World Health Organization [WHO] criteria).
    • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
    • For Part 1 only - advanced solid tumors including (but not limited to) non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastroesophagel junction adenocarcinoma (GEA), colorectal cancer (CRC), and renal cell carcinoma (RCC), who have progressed on all standard of care therapy and are not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
    • For Part 2 only - advanced non-squamous squamous Non-Small Cell Lung Cancer (NSCLC) that have progressed after treatment with at least:
    • Platinum-based chemotherapy and an immune checkpoint inhibitor and/or appropriate targeted therapy for an actionable gene alteration, if applicable, for non-squamous wtEGFR NSCLC (Part 2i) and squamous NSCLC (Part 2iii).
    • Platinum-based chemotherapy doublet and tyrosine kinase inhibitor(s) (TKI[s]) for non- squamous mutEGFR NSCLC (Part 2ii).
    • Must have no more than 2 lines of prior cytotoxic chemotherapy excluding adjuvant therapy and must have advanced NSCLC that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
    • For Part 3 only - Participants with advanced GEA that has progressed after treatment with at least 1 prior cytotoxic chemotherapeutic regimen for locally advanced or metastatic disease and have not received more than 2 prior lines of cytotoxic chemotherapy regimens. Participants must have progressed on
    • If applicable, an immune checkpoint inhibitor.
    • If applicable, appropriate available therapies, including HER2-directed therapies.
    • Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible.
    • For Part 4 only - Participants with history of advanced histopathologically or cytologically confirmed colorectal cancer (CRC) that does not harbor the BRAF V600E mutation and are not dMMR+/MSI-Hi with progression on:
    • A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine).
    • Oxaliplatin.
    • Irinotecan.
    • If applicable, anti-EGFR (including, but not limited to cetuximab or panitumumab).
    • If applicable, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, or aflibercept).
    • If applicable, targeted therapy
    • Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible. Prior trifluridine/tipiracil (TAS-102) or Regorafenib treated participants are eligible.
    • For Part 5 only - participants with advanced histologically or cytologically confirmed solid tumors characterized by MET amplification who are not amenable to surgical resection and who have disease progression after at least one prior systemic therapy and/or who have no satisfactory alternative treatment options. Participants who are intolerant to standard treatment are eligible.
    • For Part 6 only - Participants with advanced histologically or cytologically confirmed solid tumors harboring MET mutations including: mutations in the tyrosine kinase domain, the juxtamembrane region and the extracellular domain (as locally determined by next-generation sequencing (NGS) or a validated qPCR on tissue), who are not amenable to surgical resection and who have disease progression after at least one prior systemic therapy and/or who have no satisfactory alternative treatment options.
    • Intolerant to the standard treatment are eligible
    • For Part 7 (CRC combination) only: Participants with history of advanced histopathologically or cytologically confirmed CRC that does not harbor the mutation and are not dMMR+/MSI-H with progression on:
    • A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine)
    • Oxaliplatin
    • Irinotecan
    • If applicable, anti-EGFR (including, but not limited to cetuximab or panitumumab)
    • If applicable, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, or aflibercept)
    • If applicable, targeted therapy Participants who are considered ineligible for or are intolerant of standard therapy per investigator are eligible. Participants treated previously with TAS-102 or regorafenib are not eligible.
    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
    • Laboratory values meeting the criteria outlined in the protocol.
    Exclusion criteria
    • History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or on screening chest CT scan..
    • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
    • History of clinically significant, intercurrent lung-specific illnesses, as noted in the protocol.
    • For Part 7 only: Prior TAS-102 or regorafenib treated participants are not eligible.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Irene Moreno
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer
    Solid Tumor
    Gastroesophageal
    Bowel (Colorectal)
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Bernard Doger de Speville
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer
    Solid Tumor
    Gastroesophageal
    Bowel (Colorectal)
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Manish Sharma
    Status
    Recruiting
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer
    Solid Tumor
    Gastroesophageal
    Bowel (Colorectal)