Trial Title:
Amivantamab With Tyrosine Kinase Inhibitors (TKI) for Advanced NSCLC With ALK, ROS1, or RET Alterations
NCT ID:
NCT05845671
Condition:
Lung Cancer
Non Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Amivantamab-vmjw
Antibodies, Bispecific
Conditions: Keywords:
ALK
ROS1
RET
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Amivantamab 1050mg
Description:
Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and
MET.
In in vitro and in vivo studies amivantamab was able to disrupt EGFR and MET signaling
functions through blocking ligand binding and, in exon 20 insertion mutation models,
degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells
also allows for targeting of these cells for destruction by immune effector cells, such
as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity
(ADCC) and trogocytosis mechanisms, respectively.
Arm group label:
Dose Finding (Safety Lead-In) Cohort (<80 kg)
Other name:
JNJ-61186372
Intervention type:
Drug
Intervention name:
Amivantamab 1400mg
Description:
Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and
MET.
In in vitro and in vivo studies amivantamab was able to disrupt EGFR and MET signaling
functions through blocking ligand binding and, in exon 20 insertion mutation models,
degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells
also allows for targeting of these cells for destruction by immune effector cells, such
as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity
(ADCC) and trogocytosis mechanisms, respectively.
Arm group label:
Dose Finding (Safety Lead-In) Cohort (≥80 kg)
Other name:
JNJ-61186372
Intervention type:
Drug
Intervention name:
Amivantamab (to be determined)
Description:
Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and
MET.
In in vitro and in vivo studies amivantamab was able to disrupt EGFR and MET signaling
functions through blocking ligand binding and, in exon 20 insertion mutation models,
degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells
also allows for targeting of these cells for destruction by immune effector cells, such
as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity
(ADCC) and trogocytosis mechanisms, respectively.
Dose will be determine after the Safety Lead-In
Arm group label:
Dose Expansion Cohort (<80 kg)
Other name:
JNJ-61186372
Intervention type:
Drug
Intervention name:
Amivantamab (to be determined)
Description:
Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and
MET.
In in vitro and in vivo studies amivantamab was able to disrupt EGFR and MET signaling
functions through blocking ligand binding and, in exon 20 insertion mutation models,
degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells
also allows for targeting of these cells for destruction by immune effector cells, such
as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity
(ADCC) and trogocytosis mechanisms, respectively.
Dose will be determine after the Safety Lead-In
Arm group label:
Dose Expansion Cohort (≥80 kg)
Other name:
JNJ-61186372
Summary:
Although non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase
(ALK), c-ros oncogene 1(ROS1), and ret proto-oncogene (RET) gene fusions initially
respond well to tyrosine kinase inhibitor (TKI) therapies, acquired resistance is
inevitable. In many of these cases, increased activation of the erythroblastic leukemia
viral oncogene homologue (ERBB) or cMet pathways appears to be a bypass signaling
mechanism that allows these cancer cells to circumvent the selective pressure from TKIs.
Recent data have suggested that these pathways compensate for each other in situations
where one pathway is inhibited, leading to "kinase switch" drug resistance. Thus, the
expected inhibition of both pathways via treatment with the amivantamab and combination
TKI combination may improve overall efficacy by limiting the compensatory pathway
activation.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Provision to sign and date the informed consent form.
2. Stated willingness to comply with all study procedures and be available for the
duration of the study.
3. Participant is ≥ 18 years of age.
4. Participant has histologic or cytologic confirmation of locally advanced
(unresectable) or metastatic NSCLC with a known (and documented) ALK, ROS1, or RET
fusion based on approved diagnostic testing methods specified below
1. IHC: For ALK NSCLC only using the ALK D5F3 antibody
2. FISH with ≥15% of 100 cells sampled constituting positivity
3. NGS using a CLIA-certified test
5. Participants must have clinical progression on at least one prior FDA-approved TKI.
They must be on a TKI at the same dose for at least 8 weeks without radiographic
progression or clinical intolerance of the TKI prior to enrolling on this study.
TKIs that will be considered include (but not limited to):
1. ALK fusions - alectinib, brigatinib, lorlatinib
2. ROS1 fusions - entrectinib, lorlatinib
3. RET fusions - selpercatinib, pralsetinib
6. Participants must have at least 1 measurable lesion by RECIST v1.1 criteria using
computed tomography (CT) scan or magnetic resonance imaging (MRI).
1. Measurable CNS lesions ≥10mm must be captured as overall and intracranial
RECIST target lesions. CNS lesions 5-9mm may be included in the intra-cranial
data set alone but must be listed as non-target lesions.
2. Measurable, treated brain metastases (≥ 10mm) growing after whole-brain
radiotherapy (WBRT) or resection are allowed as target lesions, but lesions
growing after stereotactic radiosurgery (SRS) are allowed as target lesions
only if radiation necrosis or pseudoprogression is ruled out.
7. Participant has an Eastern Cooperative Oncology Group (ECOG) score of 0-2
8. Participant has a life expectancy of greater than 12 weeks, per investigator
discretion.
9. Participant can ingest oral medications.
10. Participant has received the final dose of any of the following
treatments/procedures*† with the specified minimum intervals before the first dose
of study drug (unless in the opinion of the Sponsor-Investigator, the medication
will not interfere with the study or compromise participant safety).
Chemotherapy‡ 21 days Antibody-drug conjugate (ADC) 28 days Immune checkpoint
inhibitors (ICI) 28 days Locally ablative radiotherapy§ 28 days Palliative
radiotherapy§ 14 days Major surgery 28 days
11. Participant has adequate organ function as determined by the following laboratory
values.
Absolute neutrophil count (ANC)* ≥ 1,500/mm3 (≥ 1.5 x 109/L) Platelets† ≥ 75,000/mm3
(≥ 75 x 109/L) Hemoglobin† ≥ 9 g/dL Renal function: Serum creatinine ≤ 1.5 x upper
limit normal (ULN) OR creatinine clearance ≥50 mL/min/1.73 m2 via Cockcroft-Gault
Liver transaminases (ALT/AST) ≤ 3 x ULN
- 5 x ULN, if liver metastases are present on screening Bilirubin ≤ 1.5 x ULN
- 3.0 x ULN, if patient has Gilbert's disease Amylase and lipase ≤ 1.5 x ULN
- Participants cannot be receiving growth factor support using
granulocyte-stimulating colony factor (G-CSF) during the screening visit.
†Participants cannot receive transfusion support up to one week prior to
the screening period.
12. Female participant of childbearing potential (defined as a sexually mature woman who
has not undergone a hysterectomy [surgical removal of the uterus] or bilateral
oophorectomy [surgical removal of both ovaries], or if ≥ 45 years old, has not been
naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at
any time during the preceding 24 consecutive months]) must:
1. Have 1 negative pregnancy test as verified by an Investigator prior to starting
study therapy. This applies even if the subject practices true abstinence* from
heterosexual contact.
2. Either commit to true abstinence* from heterosexual contact (which must be
reviewed on a monthly basis) or agree to use and be able to comply with a
barrier method plus a hormonal method of contraception without interruption 28
days prior to starting investigational product, during the study therapy
(including dose interruptions), and for 3 months after discontinuation (or
longer if required by local requirements) of study therapy. The method of
contraception must be a barrier method plus a hormonal method to prevent
pregnancy.
3. Participants must agree to continue contraception throughout the study and
continuing through 3 months after the last dose of study drug. Note: If the
childbearing potential changes after start of the study (e.g., woman who is not
heterosexually active becomes active, premenarchal woman experiences menarche)
the woman must begin a highly effective method of birth control, as described
above.
4. A woman of childbearing potential must have a negative serum or urine (b- human
chorionic gonadotropin [b-hCG]) at Screening.
5. A woman must agree not to donate eggs (ova, oocytes) for the purposes of
assisted reproduction during the study and for 6 months after receiving the
last dose of study drug.
6. A female participant must agree not to be pregnant, or breast-feeding, or
planning to become pregnant while enrolled in this study or within 3 months
after the last dose of study treatment.
13. A man who is sexually active with a woman of childbearing potential must agree to
use a condom with spermicidal foam/gel/film/cream/suppository and his partner must
also be practicing a highly effective method of contraception (i.e., established use
of oral, injected or implanted hormonal methods of contraception; placement of an
intrauterine device [IUD] or intrauterine system [IUS]). If the subject is
vasectomized, he must still use a condom (with or without spermicide), but his
female partner is not required to use contraception. The subject must also not
donate sperm during the study and for 6 months after receiving the last dose of
study drug, even if he has undergone a successful vasectomy. True abstinence is
acceptable when this is in line with the preferred and usual lifestyle of the
subject. Note: Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria:
1. Participant has received an investigational drug within a 28-day period (or within 5
half-lives, whichever is shorter) before the first dose of study drug or is
currently participating in another interventional clinical trial, unless in the
opinion of the Sponsor-Investigator, the medication will not interfere with the
study procedures or compromise subject safety.
2. The participant cannot have ever received an EGFR TKI (e.g. osimertinib), EGFR-
directed monoclonal antibody (e.g. cetuximab), MET TKI (e.g. capmatinib, tepotinib),
MET-directed monoclonal antibody (e.g. amivantamab) or MET-directed antibody-drug
conjugate (e.g. telisotuzumab vedotin) prior to study entry. For patients with ALK
or ROS1 NSCLC, crizotinib cannot be used within 3 months of screening.
3. Participants who have progressed on a TKI in less than 8 weeks
4. The participant has evidence of neuroendocrine differentiation or small cell
transformation on the screening biopsy.
5. The patient has no evidence of an ALK, ROS1, and RET gene fusion as determined by
molecular testing. Acquired resistance mechanisms detected through NGS (or FISH)
testing for which alternative therapies exist may potentially be eligible after
consultation with the PI.
6. Participants with active, symptomatic, central nervous system disease defined as
follows:
1. Leptomeningeal disease.
2. Symptomatic cord compression from metastatic disease.
3. Untreated, symptomatic brain metastases
4. Patients with brain metastases may be potentially eligible provided that all
the following criteria are met:
i. They are not on prednisolone 20mg equivalents daily prior to enrolling in the
study.
ii. Anticonvulsants will be permitted provided the patient has been on a stable dose
for a period of 2 weeks prior to Study Day 1.
iii. Procedural interventions (such as ventriculoperitoneal shunt) greater than 12
weeks prior to Study Day 1.
iv. Palliative radiotherapy (either whole brain radiotherapy or stereotactic
radiosurgery) ≥ 28 days prior to screening.
7. Participant has active cardiovascular disease defined as the following:
a. Congestive heart failure (CHF), defined as New York Heart Association (NYHA)
class III-IV or hospitalization for CHF (any NYHA class; refer to Appendix: New York
Heart Association Criteria) within 6 months of study Day 1. b. Symptomatic acute
coronary syndrome, unstable angina, or active ischemia requiring coronary artery
stenting, angioplasty, or bypass grafting within 12 weeks prior to starting
investigational drug. c. Participant has evidence of current, uncontrolled,
clinically significant, unstable arrhythmias. Participants receiving active
anti-arrhythmic therapy are not eligible with the following exceptions: i.
Participants with atrial fibrillation medically controlled for greater than 4 weeks
prior to Study Day 1.
ii. Participants who have medical pacemakers for control of arrhythmias. d.
Participant has medically uncontrolled hypertension (defined as ≥ 160 mmHg systolic
blood pressure (SBP) and ≥ 100 mmHg diastolic blood pressure (DBP).
e. Clinically significant, acute deep vein thrombosis or pulmonary embolism within 6
months prior to first dose of study drug. Clinically non-significant thrombosis,
such as non-obstructive catheter-associated clots or incidentally detected,
asymptomatic, subsegmental pulmonary emboli are not considered exclusionary. f.
History of cerebrovascular accident or transient ischemic attack within12 weeks of
enrollment.
g. QT interval corrected by Fridericia's Formula (QTcF) prolongation to > 470ms
based on a 12-lead electrocardiogram.
8. Participant has any history of interstitial lung disease (ILD), including drug
induced ILD or radiation pneumonitis requiring treatment with prolonged steroids or
other immune suppressive agents that is unresolved or resolved within the last 3
months
9. Participant has clinical evidence or history of ongoing significant bowel
obstruction limiting oral intake, active uncontrolled malabsorption syndromes, or
any other gastrointestinal disorder or defect that would interfere with absorption,
distribution, metabolism, or excretion of the study drug and/or predispose the
subject to an increased risk of gastrointestinal toxicity.
10. Participant has an additional primary malignancy within 2 years prior to enrollment
with following exceptions:
1. Adequately resected non-melanoma skin cancer.
2. Superficial bladder tumors (Ta, Tis, or T1).
3. Adequately treated intraepithelial carcinoma of the cervix uteri.
4. Low-risk, non-metastatic prostate cancer following local treatment or ongoing
active surveillance.
5. Any other curatively treated in situ disease.
11. Participant is positive for human immunodeficiency virus (HIV), with 1 or more of
the following:
f. Receiving ART that may interfere with study treatment (consult sponsor
investigator for review of medication prior to enrollment) g. CD4 count ≤ 350 at
screening h. AIDS-defining opportunistic infection within 6 months of the start of
screening i. Not agreeing to start ART and be on ART > 4 weeks plus having HIV viral
load < 400 copies/mL at the end of 4-week period (to ensure ART is tolerated and HIV
controlled).
12. Participant has active/chronic, known, untreated, hepatitis B as demonstrated by a
positive hepatitis B surface antigen (HBsAg). Note: Subjects with a prior history of
HBV demonstrated by positive hepatitis B core antibody are eligible if they have the
following at Screening: j. Negative HBsAg. k. HBV DNA (viral load) below the lower
limit of quantification, per local testing.
l. Subjects with a positive HBsAg due to recent vaccination are eligible if HBV DNA
(viral load) is below the lower limit of quantification, per local testing.
13. Participant has active/chronic, known, untreated, hepatitis C infection as
demonstrated by a positive HCV antibody with detectable HCV viral load. Note:
Subjects with a prior history of HCV, who have completed antiviral treatment and
have subsequently documented HCV RNA below the lower limit of quantification per
local testing are eligible.
14. Participant has a concurrent and uncontrolled medical illness which would preclude
study conduct and assessment, including, but not limited to the following medical
conditions: an active infection requiring systemic therapy, bleeding disorder,
clinically unstable ophthalmologic condition, diabetes mellitus with end-organ
damage, pulmonary diseases, or alcoholic liver disease.
15. Participant is a pregnant or lactating woman.
16. Participant has a history of severe allergic reactions to any of the study
intervention components.
17. Participant has a medical or psychiatric condition, which might compromise their
ability to give written informed consent or to comply with the study protocol visits
and procedures.
18. Participant has immune-mediated rash from checkpoint inhibitors that has not
resolved prior to enrollment.
19. Use of live or live-attenuated vaccines within 30 days of screening.
20. Participant has significant reversible toxicities from prior anti-cancer therapy
that have not recovered to Grade 1 or baseline (higher grades of alopecia and
neuropathy up to Grade 2 will be permitted).
21. Participant had major surgery excluding placement of vascular access or tumor
biopsy, or had significant traumatic injury within 4 weeks before enrollment, or
will not have fully recovered from surgery, or has surgery planned during the time
the participant is expected to participate in the study. Note: Participants with
planned surgical procedures to be conducted under local anesthesia may participate.
Gender:
All
Minimum age:
18 Years
Maximum age:
90 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Colorado Research Center
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Febin Elias
Phone:
303-724-9459
Email:
febin.elias@cuanschutz.edu
Investigator:
Last name:
Ross Camidge
Email:
Sub-Investigator
Investigator:
Last name:
Paul Bunn
Email:
Sub-Investigator
Investigator:
Last name:
Tejas Patil
Email:
Principal Investigator
Investigator:
Last name:
Candice Rossi
Email:
Sub-Investigator
Investigator:
Last name:
Erin Schenk
Email:
Sub-Investigator
Investigator:
Last name:
Benjamin Yoder
Email:
Sub-Investigator
Investigator:
Last name:
Eliza Miller
Email:
Sub-Investigator
Facility:
Name:
Outpatient CTRC
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Febin Elias
Phone:
303-724-9459
Email:
febin.elias@cuanschutz.edu
Facility:
Name:
UCHealth Metro Denver
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Febin Elias
Phone:
303-724-9459
Email:
febin.elias@cuanschutz.edu
Investigator:
Last name:
Benjamin Yoder
Email:
Sub-Investigator
Facility:
Name:
University of Michigan Rogel Cancer Center
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dhaman Bansal
Email:
shbansl@med.umich.edu
Investigator:
Last name:
Angel Qin, MD
Email:
Principal Investigator
Start date:
July 11, 2023
Completion date:
January 2028
Lead sponsor:
Agency:
University of Colorado, Denver
Agency class:
Other
Collaborator:
Agency:
Janssen Research & Development, LLC
Agency class:
Industry
Source:
University of Colorado, Denver
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05845671
