Trial Title:
Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)
NCT ID:
NCT06311214
Condition:
Advanced Malignant Solid Neoplasm
Metastatic Malignant Solid Neoplasm
Conditions: Official terms:
Neoplasms
Trastuzumab
Camptothecin
Irinotecan
Antibodies
Immunoglobulins
Immunoconjugates
Sacituzumab govitecan
Trastuzumab deruxtecan
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Cohort A (sacituzumab govitecan)
Arm group label:
Cohort B (enfortumab vedotin)
Arm group label:
Cohort C (trastuzumab deruxtecan)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Cohort A (sacituzumab govitecan)
Arm group label:
Cohort B (enfortumab vedotin)
Arm group label:
Cohort C (trastuzumab deruxtecan)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Cohort A (sacituzumab govitecan)
Arm group label:
Cohort B (enfortumab vedotin)
Arm group label:
Cohort C (trastuzumab deruxtecan)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Cohort C (trastuzumab deruxtecan)
Other name:
EC
Intervention type:
Other
Intervention name:
Electronic Health Record Review
Description:
Undergo review of SOC RNA testing results
Arm group label:
Screening (record review, IHC assay)
Intervention type:
Drug
Intervention name:
Enfortumab Vedotin
Description:
Given IV
Arm group label:
Cohort B (enfortumab vedotin)
Other name:
AGS 22ME
Other name:
AGS-22M6E
Other name:
Anti-Nectin 4 ADC ASG-22CE
Other name:
Anti-nectin-4 Monoclonal Antibody-Drug Conjugate AGS-22M6E
Other name:
ASG 22CE
Other name:
ASG-22CE
Other name:
ASG22CE
Other name:
Enfortumab Vedotin-ejfv
Other name:
Padcev
Intervention type:
Other
Intervention name:
Immunohistochemistry Staining Method
Description:
Undergo IHC assay
Arm group label:
Screening (record review, IHC assay)
Other name:
Cell/Tissue, Immunohistochemistry
Other name:
IHC
Other name:
Immunohistochemistry
Other name:
Immunohistochemistry (IHC)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Cohort A (sacituzumab govitecan)
Arm group label:
Cohort B (enfortumab vedotin)
Arm group label:
Cohort C (trastuzumab deruxtecan)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Cohort C (trastuzumab deruxtecan)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNV Scan
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Biological
Intervention name:
Sacituzumab Govitecan
Description:
Given IV
Arm group label:
Cohort A (sacituzumab govitecan)
Other name:
hRS7-SN38 Antibody Drug Conjugate
Other name:
IMMU 132
Other name:
IMMU-132
Other name:
IMMU132
Other name:
RS7 SN38
Other name:
RS7-SN38
Other name:
RS7SN38
Other name:
Sacituzumab Govitecan-hziy
Other name:
Trodelvy
Intervention type:
Biological
Intervention name:
Trastuzumab Deruxtecan
Description:
Given IV
Arm group label:
Cohort C (trastuzumab deruxtecan)
Other name:
DS-8201
Other name:
DS-8201a
Other name:
Enhertu
Other name:
Fam-trastuzumab Deruxtecan-nxki
Other name:
T-DXd
Other name:
WHO 10516
Summary:
This phase II ADC MATCH screening and multi-sub-study treatment trial is evaluating
whether biomarker-directed treatment with one of three antibody-drug conjugates (ADCs)
(sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan) works in treating
patients with solid tumor cancers that have high expression of the Trop-2, nectin-4, or
HER2 proteins and that may have spread from where they first started (primary site) to
nearby tissue, lymph nodes, or distant parts of the body (advanced) or to other places in
the body (metastatic). Precision medicine is a form of medicine that uses information
about a person's genes, proteins, and environment to prevent, diagnose, or treat disease
in a way that is tailored to the patient. ADCs such as sacituzumab govitecan, enfortumab
vedotin, and trastuzumab deruxtecan are monoclonal antibodies attached to biologically
active drugs and are a form of targeted therapy. Sacituzumab govitecan is a monoclonal
antibody, called sacituzumab, linked to a drug called govitecan. Sacituzumab attaches to
a protein called Trop-2 on the surface of tumor cells and delivers govitecan to kill
them. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer
drug called vedotin. It works by helping the immune system to slow or stop the growth of
tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a
targeted way and delivers vedotin to kill them. Trastuzumab deruxtecan is composed of a
monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called
deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and
delivers deruxtecan to kill them. Personalized treatment with sacituzumab govitecan,
enfortumab vedotin, or trastuzumab deruxtecan may be an effective treatment option for
patients with advanced or metastatic solid tumors that screen positive for high
expression of Trop-2, nectin-4, or HER2, respectively.
Detailed description:
PRIMARY OBJECTIVES:
I. To evaluate the proportion of patients with expression of targets of interest (TOIs)
by ribonucleic acid (RNA) testing who have expression of the TOI protein by
immunohistochemistry (IHC). (ADC MATCH screening protocol) II. To evaluate the response
profile of patients with advanced/metastatic solid tumors and high TOI protein expression
to matched ADCs. (ADC MATCH treatment cohorts)
SECONDARY OBJECTIVES:
I. To determine the proportion of patients with high validated TOI protein expression who
receive treatment on ADC MATCH. (ADC MATCH screening protocol) II. To evaluate the
proportion of patients with advanced/metastatic solid tumors who are alive and
progression free at 6 months of treatment with targeted ADC. (ADC MATCH treatment
cohorts) III. To evaluate time until death or disease progression. (ADC MATCH treatment
cohorts) IV. To determine progression-free survival (PFS) compared to prior line of
therapy (PFS2/PFS1). (ADC MATCH treatment cohorts) V. To determine the correlation of RNA
and protein expression of TOIs. (ADC MATCH treatment cohorts) VI. To determine temporal
tumor heterogeneity by comparing RNA/protein expression of TOIs on archival samples
versus fresh biopsies. (ADC MATCH treatment cohorts) VII. To identify potential
predictive biomarkers, including target expression (RNA and protein) and other molecular
features (deoxyribonucleic acid [DNA], RNA, protein, immune markers). (ADC MATCH
treatment cohorts) VIII. To determine pharmacodynamic changes in the tumor and
microenvironment. (ADC MATCH treatment cohorts)
EXPLORATORY OBJECTIVE:
I. To determine mechanisms of acquired resistance. (ADC MATCH treatment cohort)
OUTLINE:
SCREENING STEP 1: Patients who have previously undergone standard of care (SOC) RNA
testing have the results of their SOC RNA testing reviewed. Patients whose tumor
expresses an appropriate TOI by RNA testing proceed to screening step 2.
SCREENING STEP 2: Patients have TOI expression testing at the protein level by IHC assay
performed on previously collected tissue. Patients with high Trop-2 protein expression
are assigned to Cohort A. Patients with high nectin-4 protein expression are assigned to
Cohort B. Patients with high HER2 protein expression are assigned to cohort C.
COHORT A: Patients receive sacituzumab govitecan intravenously (IV) over 1-3 hours on
days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease
progression or unacceptable toxicity. Patients also undergo computed tomography (CT)
and/or magnetic resonance imaging (MRI) throughout the trial, undergo biopsy after
enrollment to cohort but prior to treatment and again on study, and undergo collection of
blood samples after enrollment to cohort but prior to treatment. Patients may optionally
undergo biopsy at the time of progression and may optionally undergo collection of blood
samples on study and at the time of progression.
COHORT B: Patients receive enfortumab vedotin IV over 30 minutes on days 1, 8, and 15 of
each cycle. Cycles repeat every 28 days in the absence of disease progression or
unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial, undergo
biopsy after enrollment to cohort but prior to treatment and again on study, and undergo
collection of blood samples after enrollment to cohort but prior to treatment. Patients
may optionally undergo biopsy at the time of progression and may optionally undergo
collection of blood samples on study and at the time of progression.
COHORT C: Patients receive trastuzumab deruxtecan IV over 90 minutes on day 1 of each
cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable
toxicity. Patients also undergo CT and/or MRI throughout the trial, undergo biopsy after
enrollment to cohort but prior to treatment and again on study, and undergo collection of
blood samples after enrollment to cohort but prior to treatment. Patients also undergo
echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and on study.
Patients may optionally undergo biopsy at the time of progression and may optionally
undergo collection of blood samples on study and at the time of progression.
At the time that a confirmed objective response is observed for a specific tumor type in
any cohort, that tumor type may be expanded into a separate tumor-specific expansion
cohort, with up to 2 expansion cohorts allowed per treatment cohort. At the time of
disease progression, patients with expression of additional TOIs may be re-screened and
assigned to receive treatment in up to 2 of the other treatment cohorts.
After completion of study treatment, patients are followed up at 30 days then every 3
months in years 1-2 and every 6 months in year 3.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- SCREENING PROTOCOL INCLUSION CRITERIA:
- Patients must have histologically confirmed solid tumor requiring therapy and meet
one of the following criteria:
- Patients who have progressed or cannot receive standard therapy that has been
shown to prolong overall survival (OS) will be eligible, if other eligibility
criteria are met. If the patient is currently receiving therapy without
progression, the clinician must have assessed that the current therapy is no
longer benefiting the patient, or that the patient is not tolerating the
therapy. Patients can be screened on ADC MATCH if they are on first-line
treatment and expected to need a treatment change within 3 months, and ADC
MATCH is felt to be appropriate next line therapy OR
- Patients with disease for which no standard treatment exists that has been
shown to prolong OS NOTE: Patients can be on therapy at the time of initiating
the screening protocol if the patient is interested in treatment on ADC MATCH
upon progression, and the physician deems this appropriate
- Patient must have undergone RNA testing in a Clinical Laboratory Improvement Act
(CLIA) environment. Patients who have high TOI RNA expression will have confirmation
of TOI expression by CLIA IHC assay at MD Anderson Cancer Center (MDACC). Only
patients with confirmed TOI protein expression will be eligible for assignment to a
treatment cohort. Retrospective confirmation in another central laboratory may also
be performed
- Patients must be willing to undergo mandatory pre-treatment and on-treatment tumor
biopsies
- Patients must have measurable disease
- Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available
on the use of the Cancer Therapy Evaluation Program (CTEP) investigational new drug
(IND) agents to be used in the study in patients < 18 years of age, children are
excluded from this study
- Eastern Cooperative Oncology Group performance status ≤ 1 (Karnofsky ≥ 70%)
- No history of transfusion dependence
- No history of persistent bone marrow suppression (absolute neutrophil count ≥
1,500/mL and platelets ≥ 100,000/mL not attributable to active therapy; patients
currently on bone marrow suppressive therapy can undergo assessment for the
screening protocol but cannot be treated on any of the treatment cohorts unless bone
marrow suppression is reversed off the suppressive therapy)
- Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert
syndrome is allowed if total bilirubin is ≤ 3 × ULN
- Aspartate transaminase (serum glutamic-oxaloacetic transaminase [SGOT])/alanine
transaminase (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 × institutional
ULN. Transaminases up to 5 × ULN in the presence of liver metastases are not allowed
to initiate the screening protocol but are allowed for the treatment cohorts
- Creatinine ≤ institutional ULN OR glomerular filtration rate ≥ 60 mL/min/1.73 m^2
for patients with creatinine levels above institutional normal unless data exists
supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73
m^2
- Patients must have albumin ≥ 3 g/dL
- Human immunodeficiency virus-infected patients on effective anti-retroviral therapy
with undetectable viral load within 6 months are eligible for this study
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational agents are eligible for this study
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this study, patients should be class 2B or better
- Women of childbearing potential must have a negative human serum pregnancy test
result at the screening protocol
- The effects of the study drugs on the developing human fetus are unknown. For this
reason and because investigational agents as well as other therapeutic agents used
in this trial are known to be teratogenic, women of childbearing potential and men
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of study participation,
and for 6 months after completion of study drug administration (unless otherwise
indicated in the eligibility section of the treatment cohort protocols). Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately.
Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to study entry, for the duration of study participation, and for
6 months after completion of study drug administration
- Ability to understand and the willingness to sign a written informed consent
document
- ADDITIONAL INCLUSION CRITERIA FOR TREATMENT COHORTS:
- Women of childbearing potential must have a negative serum pregnancy test result at
treatment cohort screening
- Hemoglobin > 9.0 g/dL
- Leukocytes ≥ 3000/mL
- Absolute neutrophil count ≥ 1,500/mL
- Platelets ≥ 100,000/mL
- Patient must be willing to sign the relevant treatment cohort consent form
- COHORT A INCLUSION CRITERIA:
- Patients must fulfill all the eligibility criteria outlined in the ADC MATCH
screening protocol at the time of treatment cohort A registration
- Patient must have high Trop-2 protein expression (IHC 2+ or 3+) as determined by the
MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay
- Patients who have Trop-2 IHC testing without RNA testing or who have Trop-2 IHC
2 or 3+ expression but do not have Trop-2 expression detected on RNA testing
will not be eligible for the trial.
- Patients who have Trop-2 RNA expression and Trop-2 IHC 2+ or 3+ on another
Trop-2 IHC test will undergo Trop-2 testing with the integral MDACC IHC assay
- Patients who already have RNA expression testing demonstrating Trop-2 RNA
expression as well as IHC testing on the MDACC CLIA lab platform will be
eligible for enrollment after review of results by the Precision Oncology
Decision Support team without having to repeat Trop-2 IHC results as part of
pre-screening. Patients who have had TROP2 2+ testing result performed outside
of MDACC will have to undergo MDACC TROP2 IHC analysis before enrollment
- COHORT B INCLUSION CRITERIA:
- Patients must fulfill all the eligibility criteria outlined in the ADC MATCH
screening protocol at the time of treatment cohort B registration
- Patient must have high Nectin-4 protein expression (IHC 2+ or 3+) as determined by
the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay
- COHORT C INCLUSION CRITERIA:
- Patients must fulfill all the eligibility criteria outlined in the ADC MATCH
screening protocol at the time of treatment cohort C registration
- Patient must have HER2 protein expression (IHC 2+ or 3+) as determined by the MD
Anderson Cancer Center (MDACC) IHC assay
- Patients who have HER2 IHC testing without RNA testing or who have HER2 IHC 2
or 3+ expression but do not have HER2 expression detected on RNA testing will
not be eligible for the trial
- Patients who have HER2 RNA expression and HER2 IHC 3+ or 2+ on another HER2 IHC
test will undergo HER2 testing with the integral MDACC IHC assay
- Patients who already have RNA expression testing demonstrating HER2 RNA
expression as well as IHC testing on the MDACC CLIA lab platform will be
eligible for enrollment after review of results by the Precision Oncology
Decision Support team without having to repeat HER2 IHC results as part of
pre-screening. Patients who have had HER2 2+ testing result performed outside
of MDACC will have to undergo MDACC HER2 IHC analysis before enrollment
- Women of childbearing potential must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry, for the
duration of study participation, and for 7 months after completion of study drug
administration. Women should not breastfeed during the study treatment period and
for 7 months after completion of study drug administration. Should a woman become
pregnant or suspect she is pregnant while she or her partner is participating in
this study, she should inform her treating physician immediately. Men treated or
enrolled on this protocol must also agree to use adequate contraception prior to
study entry, for the duration of study participation, and for 4 months after
completion of study drug administration
Exclusion Criteria:
- SCREENING PROTOCOL EXCLUSION CRITERIA:
- Patients with histologically documented non-small cell lung cancer, triple negative
breast cancer, urothelial cancer, head and neck cancer, hormone receptor-positive
breast cancer, small cell lung cancer, or endometrial cancer
- Patients with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease. Patients with treated brain metastases are eligible if
follow-up brain imaging 4 weeks after central nervous system-directed therapy shows
no evidence of progression
- Clinically significant cardiovascular condition including: (1) history of congestive
heart failure (New York Health Association class > 2), (2) any history of unstable
angina, (3) myocardial infraction within the past 12 months, or (4) any history of
supraventricular arrhythmia or ventricular arrhythmia requiring treatment or
intervention
- History or presence of abnormal electrocardiogram (ECG) that, in the investigator's
opinion, is clinically meaningful
- Active or chronic corneal disorder including, but not limited to, Sjogren's
syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal
transplantation, active herpetic keratitis, and/or active ocular conditions
requiring ongoing treatment/monitoring such as wet age-related macular degeneration
requiring intravitreal injections, active diabetic retinopathy with macular edema,
presence of papilledema, and acquired monocular vision
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to the ADCs used in the study
- History of interstitial lung disease or pneumonitis requiring steroid therapy
- Grade 2 or greater peripheral neuropathy
- Patients requiring the use of full dose coumarin-derivative anticoagulants such as
warfarin. Low molecular weight heparin is permitted for prophylactic or therapeutic
use. Factor X inhibitors are permitted
- Note: Warfarin may not be started while enrolled in the treatment cohorts.
Stopping the anticoagulation for biopsy should be per site standard operating
practice
- Pregnant women are excluded from the study because the study drugs are
investigational or approved agents with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for AEs in
nursing infants secondary to treatment of the mother with any of the study drugs,
breastfeeding should be discontinued if the mother is treated with any of the study
drug
- ADDITIONAL EXCLUSION CRITERIA FOR TREATMENT COHORTS:
- Patients must have adequate washout from prior therapy at the time of study
treatment initiation: 4 weeks from major surgery; 4 weeks from antibody-based
therapy; 2 weeks or 5 half-lives (whichever is shorter) from any targeted therapy or
small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from
chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive
radiotherapy, mitomycin C, and nitrosoureas); and 4 weeks from radiation therapy.
Patients should have received no more than 3 prior lines of chemotherapy.
Testosterone suppression as supportive treatment for castration-resistant prostate
cancer and ovarian suppression in premenopausal patients with breast cancer that
have supportive treatment and not anticancer treatment role (with luteinizing
hormone-releasing hormone analogs) will be allowed if the patients were on these
supportive treatments before starting the study. Use of bone-modifying medications
(bisphosphonates or denosumab) will be allowed. Palliative radiotherapy of
non-target lesions is permitted, but presence of new or worsening metastases will be
considered progressive disease. If there is clear evidence of clinical benefit,
study treatment may be continued 2 weeks after completion of palliative radiotherapy
to lesions that are non-target lesions. Patients can be on therapy during treatment
cohort screening
- Patients who are currently receiving any other investigational agent(s)
- Received systemic therapy with corticosteroids at > 20 mg/day prednisone or
equivalent within 1 week prior to cycle 1 day 1
- Patients who have not recovered from AEs due to prior anticancer therapy (i.e., have
residual toxicities > grade 1) with the exception of alopecia
- When the corrected QT interval (QTc) by Fridericia's formula is < 120 ms, > 450 ms
in males and > 470 ms in females. When the QTc by Rautaharju's formula is ≥ 120 ms,
> 450 ms in males and > 470 ms in females
- Uncontrolled infection requiring intravenous antibiotic, antiviral, or antifungal
use
- Received a live, attenuated vaccine within 30 days prior to cycle 1 day 1. Enrolled
patients should not receive live vaccine during the study. Non-live COVID vaccines
will be allowed on study, but it is recommended to avoid their use during the first
treatment cycle (from 3 days prior to cycle 1 day 1 through cycle 2 day 3)
- Patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements
- Other concurrent medical or psychiatric conditions that, in the investigator's
opinion, may be likely to confound study interpretation or prevent completion of
study procedures and follow-up examinations
- COHORT A EXCLUSION CRITERIA:
- Patients with histologically documented advanced colorectal cancer
- Patients who have received growth factor support within 2 weeks of study treatment
initiation
- Coadministration of sacituzumab govitecan (IMMU-132) with inhibitors of UGT1A1 may
increase systemic exposure to the active metabolite, SN-38. UGT1A1 inhibitors should
not be administered concomitantly with sacituzumab govitecan (IMMU-132) unless there
are no therapeutic alternatives
- Prior topoisomerase 1 inhibitor treatment
- Prior treatment with a Trop-2-targeting ADC
- Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)
or gastrointestinal (GI) perforation within 6 months of treatment cohort A
registration
- COHORT B EXCLUSION CRITERIA:
- Patients with histologically documented advanced breast cancer, lung cancer, gastric
cancer, gastroesophageal junction, or esophageal cancer
- Concomitant use of strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4.
Washout period is 2 weeks prior to study treatment initiation
- History of uncontrolled diabetes mellitus within 3 months before the first dose of
study treatment. Uncontrolled diabetes mellitus is defined as hemoglobin A1c ≥ 8% or
hemoglobin A1c between 7 and < 8% with associated diabetes symptoms (polyuria or
polydipsia) that are not otherwise explained
- Known active keratitis or corneal ulcerations. Patients with superficial punctate
keratitis are allowed if the disorder is being adequately treated
- Known hypersensitivity to enfortumab vedotin or to any excipient in the drug
formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and
polysorbate 20), or known hypersensitivity to biopharmaceutical produced in Chinese
hamster ovary cells
- COHORT C EXCLUSION CRITERIA:
- Patients with histologically documented advanced breast cancer, lung cancer,
colorectal cancer (CRC), gastric cancer, or pancreatic cancer
- Previous treatment with topoisomerase I inhibitors as a free form or as other
formulations, and ADCs with topoisomerase I inhibitor payloads
- Patients receiving treatment with chloroquine or hydroxychloroquine are not allowed
to participate in the study, unless there is a washout period of at least 14 days
prior to the first dose of study drug
- History of non-infectious pneumonitis/interstitial lung disease (ILD), current ILD,
or where suspected ILD that cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant illnesses including, but not
limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3
months of initiation of study drug, severe asthma, severe chronic obstructive
pulmonary disease, restrictive lung disease, pleural effusion etc.)
- Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid
arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of
pulmonary involvement at the time of screening
- Prior pneumonectomy
- Left ventricular ejection fraction (LVEF) < 40%
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
December 20, 2024
Completion date:
October 31, 2027
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06311214
