This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and
preliminary efficacy of ABBV-399 as monotherapy and in combination with osimertinib,
erlotinib, and nivolumab in participants with advanced solid tumors likely to express c-Met.
Enrollment is closed for the monotherapy arms, Arm A, and Arm D.
- Participant must have advanced Non-Small Cell Lung Cancer (NSCLC) that is not amenable
to surgical resection or other approved therapeutic options that have demonstrated
- Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0
- Participant must have measurable disease per Response Evaluation Criteria In Solid
Tumors (RECIST) version 1.1.
- Participant has archived diagnostic formalin-fixed paraffin embedded (FFPE) tumor
tissue confirmed available for analyses.
- Participant has adequate bone marrow, renal, and hepatic function.
- Women of childbearing potential must have a negative serum pregnancy test at baseline.
- Participants in the combination therapy arms A and D must be eligible to receive
erlotinib, or nivolumab per most locally approved labeling, or at the discretion of
- Participants in the combination therapy Arm E must satisfy following criteria.
- Participant must have metastatic/locally advanced nonsquamous NSCLC with
documented Epidermal Growth Factor Receptor (EGFR) mutation(s) del19 or L858R,
with or without T790M mutation, and none of the EGFR mutations known to be
resistant to osimertinib.
- Participant must have received at least 1 but no more than 2 prior regimens, one
of which must have contained osimertinib. Participant must have had disease
progression while on osimertinib. Only 1 prior regimen may have contained
- Participant must have available post-progression tumor tissue for central c-Met
immunohistochemistry (IHC) testing.
- Participant has adequate bone marrow function.
- Participant has received anticancer therapy including chemotherapy, 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.
- Participant has uncontrolled metastases to the central nervous system (CNS) based on
head CT or MRI. Participants with brain metastases may be eligible 2 weeks after
definitive therapy to all known sites of CNS disease provided they are asymptomatic
and either off or on a non-increasing dose (in last 2 weeks) of systemic steroids and
not on anticonvulsants for seizure activity directly related to progressive CNS
- Participant has history of interstitial lung disease (ILD) or pneumonitis that
required treatment with systemic steroids, or any evidence of active ILD or
- Participant has unresolved clinically significant adverse events >= Grade 2 from prior
anticancer therapy, except for alopecia or anemia.
- Participant has had major surgery within 21 days prior to the first dose of ABBV-399.
- Participant has a clinically significant condition(s) described in the protocol.
- History of major immunologic reaction to any Immunoglobulin G (IgG) containing agent.
- Participant has any medical condition which in the opinion of the Investigator or
Medical Monitor places the participant at an unacceptably high risk for toxicities.
- Participant is a lactating or pregnant female.
- Participants with known active Coronavirus Disease - 2019 (COVID-19) infection.
Participant with signs/symptoms associated with COVID-19 infection or known exposure
to a confirmed case of COVID-19 infection during 14 days prior to Screening:
- Participants enrolled on the combination therapy phase must satisfy the above
exclusion criteria and also the following:
- Participants may not receive ABBV-399 in combination with osimertinib, erlotinib
or nivolumab if they have any medical condition which in the opinion of the
Investigator places the participant at an unacceptably high risk for toxicities
from the combination.
- Participants 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, locally injected or topical
- Known immunosuppressive disease, for example human immunodeficiency virus
infection or history of bone marrow transplant or chronic lymphocytic
- Participants may not be enrolled into the osimertinib Combination Therapy Arm E
if they have the following:
- History of hypersensitivity to active or inactive excipients of osimertinib.
- History of osimertinib dose reduction to below 80 mg once a day (QD).
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability
to swallow the formulated product, or previous significant bowel resection
that would preclude adequate absorption of osimertinib.
- Any of the following cardiac criteria: a) Mean resting corrected QT interval
(QTc) > 470 ms; b) Any clinically important abnormalities in rhythm,
conduction, or morphology of resting ECG, e.g., complete left bundle branch
block, second- or third-degree heart block, PR interval > 250 ms; c) Any
factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalemia, congenital long QT syndrome, or
any concomitant medication known to prolong the QT interval.