The goal of this clinical trial is to test ELVN-002 in people with cancers that have an abnormal HER2 gene. The main question the trial aims to answer is if ELVN-002 is safe and tolerable at different doses. A second main question is to evaluate the concentration of ELVN-002 in the blood at different doses and to see how this correlates with safety and see how the concentration of drug changes over time. The third main question is to see if ELVN-002 works to shrink cancers that have HER2 genetic abnormalities, particularly non-small cell lung cancer.
There are 4 parts to the trial. Part 1 is a dose escalation with ELVN-002 monotherapy for people with advanced stage solid tumors that have a HER2 mutation, amplification or high HER2 over-expression. Part 2 is an ELVN-002 monotherapy dose exploration where additional people may be enrolled at dose levels that have cleared the dose escalation in Part 1 to further evaluate the safety, tolerability, pharmacokinetics and clinical activity. Part 3 is a dose expansion of ELVN-002 monotherapy which will enroll up to 40 patients people with advanced stage HER2 mutant non-small cell lung cancer. Patients in Part 3 will be randomized 1:1 to receive one of two dose levels. Part 4 is a combination dose escalation where, based on the results of Part 1 and 2, a combination of ELVN-002 and either fam-trastuzumab deruxtecan-nxki (in HER2 mutant non-small cell lung cancer) or trastuzumab emtansine (in HER2 positive breast cancer) will be evaluated for safety and tolerability.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
198
University of Colorado - Anschutz Medical Campus - PPDS
Aurora, Colorado, United States
Advent Health Orlando
Orlando, Florida, United States
BRCR Medical Center Inc
Plantation, Florida, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
NEXT/Virginia Cancer Specialists
Fairfax, Virginia, United States
Incidence of dose limiting toxicities in Phase 1a monotherapy
Time frame: 21 days
Incidence of adverse events in Phase 1a monotherapy
Time frame: 24 months
incidence of laboratory abnormalities in Phase 1a monotherapy
Time frame: 24 months
incidence of ECG abnormalities in Phase 1a monotherapy
Time frame: 24 months
incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)
Time frame: 42 days
Incidence of adverse events in Phase 1a combination with T-DXd
Time frame: 24 months
incidence of laboratory abnormalities in Phase 1a combination with T-DXd
Time frame: 24 months
incidence of ECG abnormalities in Phase 1a combination with T-DXd
Time frame: 24 months
incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)
Time frame: 42 days
Incidence of adverse events in Phase 1a combination with T-DM1
Time frame: 24 months
incidence of laboratory abnormalities in Phase 1a combination with T-DM1
Time frame: 24 months
incidence of ECG abnormalities in Phase 1a combination with T-DM1
Time frame: 24 months
Incidence of adverse events in Phase 1b monotherapy
Time frame: 24 months
incidence of laboratory abnormalities in Phase 1b monotherapy
Time frame: 24 months
incidence of ECG abnormalities in Phase 1b monotherapy
Time frame: 24 months
Objective Response rate in Phase 1a monotherapy
For patients with measurable disease at baseline, confirmed response per RECIST 1.1
Time frame: 24 months
Objective response rate in Phase 1b monotherapy
Confirmed response per RECIST 1.1
Time frame: 24 months
Duration of response in Phase 1b monotherapy
The time from the first response to progression or death per RECIST 1.1
Time frame: 24 months
Brain metastases response in Phase 1b monotherapy
for patients with measurable brain metastases at baseline, the percent of patients who have a confirmed response per RECIST 1.1
Time frame: 24 months
PK parameter of area under the curve of ELVN-002 in Phase 1a monotherapy
the concentration of ELVN-002 measured in the blood over 24 hours at steady state
Time frame: 21 days
PK parameter of maximum concentration of ELVN-002 in Phase 1a monotherapy
the maximum concentration of ELVN-002 measured in the blood at any time point at steady state
Time frame: 21 days
PK parameter of terminal half life of ELVN-002 in Phase 1a monotherapy
the half life of ELVN-002 calculated from the concentration of ELVN-002 in blood
Time frame: 21 days
PK parameter of area under the curve of ELVN-002 in Phase 1b monotherapy
the concentration of ELVN-002 measured in the blood over 24 hours at steady state
Time frame: 21 days
PK parameter of maximum concentration of ELVN-002 in Phase 1b monotherapy
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Macquarie University Hospital
Westmead, New South Wales, Australia
Linear Clinical Research Limited
Nedlands, Western Australia, Australia
Blacktown Hospital
Darlinghurst, Australia
Hôpital de la Timone Centre d'essais en cancérologie de Marseille (CEPCM-CLIPP)
Marseille, Bouches-du-Rhône, France
Hôpital Pontchaillou
Rennes, Brittany Region, France
...and 29 more locations
the maximum concentration of ELVN-002 measured in the blood at any time point at steady state
Time frame: 21 days
PK parameter of terminal half life of ELVN-002 in Phase 1b monotherapy
the half life of ELVN-002 calculated from the concentration of ELVN-002 in blood
Time frame: 21 days