MC# 14-06 - A Multicenter, Phase I/Ib, Open-Label, Dose-Escalation Study of ABBV-399, an Antibody Drug Conjugate, in Subjects with Advanced Solid Tumors

  • Agent(s): ABBV-399
  • Disease Type(s): Lung-NSCLC
  • Phase(s): I
  • Drug Classification(s): Targeted Therapy, Immunotherapy, Monoclonal Antibody
  • Molecular Target(s): MET

Mechanism of Action

ABBV-399 is an antibody drug conjugate containing the potent cytotoxin monomethyl auristatin E (MMAE)


In this study, the sponsor and investigators want to learn:

  • The best way to give ABBV-399
  • How much ABBV-399 can be given safely
  • How the body handles ABBV-399
  • How to improve the treatment and/or diagnosis of cancer
Inclusion Criteria
  • Subject must be ≥ 18 years of age
  • Subjects with advanced solid tumor including but not limited to non-small cell lung cancer [NSCLC], colorectal, breast, ovarian, esophageal/gastric and head and neck.
  • Subject must have advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
    • Subjects who have refused or are intolerant of standard therapy are eligible.
    • Based on evidence gathered in this study or from external sources, the Sponsor in consultation with the Investigators may decide to limit to specific tumor types.
    • For dose-expansion: Subject must have tumor with c-Met overexpression MET exon 14 mutation or MET amplification.
  • Subject must have measurable disease per RECIST version 1.1
  • Subject has archived diagnostic formalin-fixed paraffin embedded (FFPE) tumor tissue available for analysis.
    • If a subject has local or central lab data showing c-Met overexpression, MET exon 14 mutation or MET amplification and no archival tumor tissue available, the subject may be eligible after discussion with the Medical Monitor.
  • Subject has adequate bone marrow, renal, and hepatic function as follows:
    • Bone marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3, Platelets ≥ 100,000/mm3; Hemoglobin ≥ 9.0 g/dL.
    • Renal function: Serum creatinine ≤ 1.5 × the institution's ULN range or creatinine clearance ≥ 50 mL/min measured by 24-hour urine or estimated by the Cockcroft-Gault formula.
    • Hepatic function: Bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN and albumin ≥ 3.0 g/dL. Subjects with liver metastasis may have an AST and ALT of ≤ 5.0 × the ULN.
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment. Subjects with initial positive serum pregnancy tests are eligible if it is determined through other means that the subject is not pregnant (i.e., ultrasound in cases where tumor is suspected of secreting β-HCG and resulting in a false-positive pregnancy test). Female subjects considered not of childbearing potential must be documented as being surgically sterile or post-menopausal for at least 1 year. Women of childbearing potential and men must agree to use adequate contraception (one of the following listed below-refer to Section 5.2.1 for complete list) prior to study entry, for the duration of study participation and for a period of 6 months after the last dose of study drug.
    • Vasectomy (a vasectomized male subject or a vasectomized partner of a female subject) for at least 3 months prior to study drug administration.
    • Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration.
    • Barrier method of contraception (condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository).
    • Total abstinence from sexual intercourse beginning at least one complete menstrual cycle prior to study drug administration
    • Intrauterine device (IUD, IUS)
    • Birth control implant
    • Additionally, male subject (including those who are vasectomized) whose partner is pregnant or may become pregnant must agree to use condoms for the duration of the study and for 6 months following completion of therapy.
  • Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures.

Additional Inclusion Criteria for Subjects Enrolled on the Combination Therapy Phase

  • Subjects in the combination therapy arms must meet the above inclusion criteria and be eligible to receive erlotinib, cetuximab, bevacizumab or nivolumab per most current prescribing information, or at the discretion of the Investigator.
Exclusion Criteria
  • Subject has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days, or herbal therapy within 7 days prior to the first dose of ABBV-399.
    • Palliative radiation therapy for painful bony or skin metastasis for 10 fractions or less is not subject to a washout period.
    • For approved targeted small molecules, a washout period of 5 half-lives is adequate (no washout period required for subjects currently on erlotinib)
  • Subject has known uncontrolled metastases to the central nervous system (CNS). Subjects with brain metastases are eligible after definitive therapy provided they are asymptomatic and off steroids and anticonvulsants for at least 2 weeks prior to first dose of ABBV-399.
  • Subject has unresolved adverse events ≥ Grade 2 from prior anticancer therapy except for alopecia or anemia.
  • Subject has had major surgery within 21 days prior to the first dose of ABBV-399.
  • Subject has a clinically significant uncontrolled condition(s) including but not limited to the following:
    • Grade ≥ 2 peripheral edema or lymphedema
    • Grade ≥ 2 ascites or pleural effusion.
    • Grade ≥ 2 peripheral neuropathy
    • Active uncontrolled bacterial or viral infection.
    • Symptomatic congestive heart failure.
    • Unstable angina pectoris or cardiac arrhythmia.
    • Extensive metastatic liver disease involving ≥ 50% of the liver in the judgment of the Investigator or Medical Monitor
    • Psychiatric illness/social situation that would limit compliance with the study.
  • Subject has history of major immunologic reaction to any IgG containing agent.
  • Subject has any medical condition which in the opinion of the Investigator or Medical Monitor places the subject at an unacceptably high risk for toxicities.
  • Subject is a lactating or pregnant female.

Additional Exclusion Criteria for Subjects Enrolled on the Combination Therapy Phase

  • Subjects enrolled on the combination therapy phase must satisfy the above exclusion criteria and also the following:
    • Subjects may not receive ABBV-399 in combination with erlotinib, cetuximab, bevacizumab or nivolumab if they have any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities from the combination.
      • Subjects may not receive cetuximab if they have K-ras mutation.
      • Subjects may not receive bevacizumab if they have squamous NSCLC.
      • Subjects may not receive nivolumab if they have
        • Active autoimmune disease with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis
        • Used systemic corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled or topical steroids
        • Known immunosuppressive disease, for example human immunodeficiency virus infection or history of bone marrow transplant or chronic lymphocytic leukemia.


  • Dallas, TX - Mary Crowley Cancer Research - Medical City
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Re: MC# 14-06