Description:
This study is a Phase 1/2, first-in-human, open-label, dose-escalation, and expansion study
designed to characterize the safety, tolerability, pharmacokinetics, immunogenicity, and
preliminary antitumor activity of IMGC936 administered by intravenous (IV) infusion.
Title
- Brief Title: First-in-Human Study of IMGC936 in Patients With Advanced Solid Tumors
- Official Title: A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation and Expansion Study of IMGC936 (Anti-ADAM9 Antibody Drug Conjugate) in Patients With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
IMGC936-0901
- NCT ID:
NCT04622774
Conditions
Interventions
Drug | Synonyms | Arms |
---|
IMGC936 | | IMGC936 |
Purpose
This study is a Phase 1/2, first-in-human, open-label, dose-escalation, and expansion study
designed to characterize the safety, tolerability, pharmacokinetics, immunogenicity, and
preliminary antitumor activity of IMGC936 administered by intravenous (IV) infusion.
Detailed Description
This is an open-label, dose-escalation, and expansion study to determine the Maximum
Tolerated Dose (MTD) and select the recommended phase 2 dose. Dose escalation follows a
conventional 3+3 design; successive cohorts of 3 to 6 participants each will be evaluated in
sequential escalating doses of single-agent IMGC936. Upon completion of the dose-escalation
phase of the study, following determination of the recommended Phase 2 dose (RP2D), up to 5
expansion cohorts may be opened in tumor types selected from those enrolled in dose
escalation.
Participants with relapsed or refractory, unresectable locally advanced or metastatic solid
tumors including non-squamous non-small cell lung cancer (NSCLC), triple-negative breast
cancer (TNBC), colorectal cancer (CRC), gastroesophageal cancer, or pancreatic cancer will be
enrolled.
IMGC936 is administered via intravenous (IV) infusion on Day 1 of Cycle 1 and every
subsequent 21-day cycle thereafter, at the assigned dose for each cohort during dose
escalation, and at the RP2D for expansion. Infusion duration will vary depending on dose and
participant tolerability.
Sentinel dosing will be used for the first 2 dose levels of dose escalation. The first
administration of IMGC936 in participants at the first 2 dose levels of dose escalation will
be staggered by at least 48 hours. The dose-limiting toxicity (DLT) evaluation period is 21
days. Participants may continue on study drug until disease progression, adverse event (AE)
requiring discontinuation, DLT during evaluation window, pregnancy, death, investigator
decision, lost to follow up (LTFU), major protocol deviation requiring discontinuation,
withdrawal of consent, or sponsor, investigator or regulatory agency terminates the study.
Tumor assessments are performed every 6 weeks (Q6W) while on study drug then every 12 weeks
(Q12W). Tumor assessments continue until discontinuation criteria are met. If feasible,
participants who discontinue study drug for reasons other than progressive disease (PD)
(e.g., toxicity) should continue to undergo tumor assessments Q12W as post-treatment follow
up until evidence of PD, initiation of another anticancer therapy, withdrawal of consent,
LTFU, death, or end of study. Post-treatment follow up also includes following ongoing
treatment emergent adverse events (TEAEs) until the event has resolved to baseline grade, the
event is assessed by the investigator as stable, initiations of another anticancer therapy,
withdrawal of consent, LTFU, death, or it has been determined that study drug or
participation is not the cause of the AE.
Trial Arms
Name | Type | Description | Interventions |
---|
IMGC936 | Experimental | Single-arm. IMGC936 administered every 3 weeks. | |
Eligibility Criteria
Inclusion Criteria:
1. Participants with histologically proven, relapsed or refractory, unresectable locally
advanced or metastatic non-squamous non-small cell lung cancer (NSCLC),
triple-negative breast cancer (TNBC), colorectal cancer (CRC), gastroesophageal
cancer, or pancreatic cancer for whom no therapy with demonstrated clinical benefit is
available.
1. NSCLC: Participants must have been treated with 1 to 4 prior lines of systemic
therapy with no more than 2 chemotherapy containing lines.
2. TNBC: Participants must have been treated with 1 to 4 prior lines of systemic
therapy for metastatic disease, excluding adjuvant therapies.
3. CRC: Participants must have been treated with 1 to 3 prior lines of systemic
therapy.
4. Gastroesophageal cancer: Participants must have been treated with 1 to 3 prior
lines of systemic therapy.
5. Pancreatic cancer: Participants must have been treated with 1 to 3 prior lines of
systemic therapy, with no more than 2 chemotherapy containing lines.
2. Either measurable or non-measurable disease per RECIST 1.1 and documented by computed
tomography (CT) and/or magnetic resonance imaging (MRI) obtained within 28 days of
C1D1.
- Dose escalation: Participants may have non-measurable or measurable disease
- Dose expansion: Participants must have measurable disease
3. Age ≥ 18 years old.
4. Archival formalin-fixed paraffin-embedded (FFPE) tissue must be available.
Participants may undergo a fresh tumor biopsy using a low risk, medically routine
procedure to obtain a specimen for testing if a tumor sample is not available.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. If ECOG
performance status is an inappropriate performance measurement for participant
enrollment (eg, chronically non-ambulatory), then Karnofsky performance status must be
≥ 70.
6. Life expectancy ≥ 12 weeks.
7. Acceptable laboratory parameters as follows:
- Platelet count ≥ 75 × 1000/μL without transfusion within 28 days prior to
initiation of study drug.
- Absolute neutrophil count ≥ 1.5 × 1000/μL in the absence of any growth factor
support within 21days prior to initiation of study drug.
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × upper
limit of normal (ULN); for participants with hepatic metastases, ALT and AST ≤ 5
× ULN.
- Total bilirubin ≤ 1.5 × ULN, except participants with Gilbert's syndrome, who may
enroll if the conjugated bilirubin is within normal limits.
- Estimated glomerular filtration rate (eGFR) >30mL/min/1.73m2 or an estimated
creatinine clearance of >30 mL/min.
- Urinalysis protein and white occult blood cells within normal limits.
- Negative serum pregnancy test for females of childbearing potential (FOCBP).
8. FOCBP, defined as not surgically sterilized (hysterectomy, bilateral salpingectomy,
and bilateral oophorectomy) and between menarche and 1-year post menopause, must have
a negative serum pregnancy test performed within 72 hours prior to initiation of study
drug administration. Female participants must abstain from egg donation during the
study.
9. FOCBP and male participants with partners of FOCBP must agree to use highly effective
methods of contraception, from the time of consent through 28 weeks after
discontinuation of study drug administration. Male participants must abstain from
sperm donation during the study.
10. FOCBP is not pregnant or breastfeeding, or a male participant is not expecting to
father children within the projected duration of the study, starting with screening
visit through 28 weeks after the last dose of study drug.
Exclusion Criteria:
1. Active central nervous system (CNS) disease within the last 6 months.
2. Active or chronic corneal disorders, history of corneal transplantation, or active
ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled
glaucoma, wet age-related macular degeneration requiring intravitreal injections,
active diabetic retinopathy with macular edema, macular degeneration, presence of
papilledema, and/or monocular vision.
3. Participants who had prior therapies within the specified times below:
- Systemic antineoplastic therapy at least 5 half-lives or 4 weeks (whichever is
shorter) prior to initiation of study drug.
- Mediastinal or pelvic radiation therapy within 6 weeks prior to initiation of
study drug administration. Palliative, limited field radiation for symptom
control to soft tissues, or bone lesions within 2 weeks prior to initiation of
study drug.
4. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior
therapy-related toxicities (except alopecia).
5. Clinically significant cardiovascular disease including but not limited to:
- Myocardial infarction or unstable angina within 6 months prior to initiation of
study drug.
- Stroke or transient ischemic attack within 6 months prior to initiation of study
drug.
- Current clinically significant cardiac arrhythmias, e.g., atrial fibrillation
that are not well controlled with optimal medical intervention.
- Current uncontrolled hypertension: systolic blood pressure > 160 mmHg, diastolic
blood pressure > 100 mmHg.
- Current congestive heart failure (New York Heart Association class III-IV).
- Current pericarditis or clinically significant pericardial effusion.
- Current myocarditis.
- Left ventricular ejection fraction (LVEF) of < 50% by scan
- QTc interval > 480 msec
6. Clinically significant pulmonary compromise, including pneumonia, pneumonitis, or a
requirement for supplemental oxygen (excluding for sleep apnea) or history of ≥ Grade
3 drug-induced or radiation pneumonitis.
7. Serious concurrent illness or clinically relevant active infection, including, but not
limited to the following:
- Active hepatitis B or C infection (whether or not on active antiviral therapy).
- Human immunodeficiency virus infection.
- Cytomegalovirus infection.
- Active COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory
for study entry, testing should follow local clinical practice
guidelines/standards.
- Any other concurrent infectious disease requiring IV antibiotics within 2 weeks
prior to initiation of study drug.
8. History of prior bone marrow, stem cell, or solid organ transplantation.
9. Second primary invasive malignancy that has not been in remission for greater than 2
years except nonmelanoma skin cancer; cervical carcinoma in situ on biopsy; or
squamous intraepithelial lesion on Pap smear; localized prostate cancer (Gleason score
< 6); or resected melanoma in situ.
10. Major trauma or major surgery within 4 weeks prior to initiation of study drug.
11. Any serious underlying medical or psychiatric condition that would impair the ability
of the participant to receive or tolerate the planned treatment at the study site.
12. Known hypersensitivity to any ingredient or any excipient contained in the drug
formulation
13. Vaccination with any live virus vaccine within 4 weeks prior to initiation of study
drug. Inactivated annual influenza vaccination is allowed.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | During dose escalation measure incidence and severity of Treatment Emergent Adverse Events by CTCAE v5.0 |
Time Frame: | From screening to end of study (approximately up to 2 years) for each patient |
Safety Issue: | |
Description: | Number of treatment emergent adverse events as assessed by CTCAE v5.0 |
Secondary Outcome Measures
Measure: | During dose escalation and expansion to characterize study drug concentration |
Time Frame: | There are 9 blood draw collection time points at Cycles 1 and 3, 3 blood draw time points at Cycles 2,4,5 and 6, and collection at every 3 cycles after cycle 6 until end of study (approximately up to 2 years). Each cycle is 21 days. |
Safety Issue: | |
Description: | Study drug concentration |
Measure: | During dose escalation and expansion to measure the concentration of anti-drug antibody |
Time Frame: | There are 2 collection time points at Cycles 1 and 3, 1 collection time point at Cycles 2, 4, 5 and 6, and and collection at every 3 cycles after cycle 6 until end of study (approximately up to 2 years). Each cycle is 21 days. |
Safety Issue: | |
Description: | Anti-drug antibody |
Measure: | During dose expansion describe the duration of response and progression free survival |
Time Frame: | From screening to end of study (approximately up to 2 years) for each patient |
Safety Issue: | |
Description: | Time to disease progression |
Measure: | During dose escalation to describe the objective response rate and duration of response |
Time Frame: | From screening to end of study (approximately up to 2 years) for each patient |
Safety Issue: | |
Description: | Time to disease progression |
Measure: | During dose expansion measure incidence and severity of Treatment Emergent Adverse Events by CTCAE v5.0 |
Time Frame: | From screening to end of study (approximately up to 2 years) for each patient |
Safety Issue: | |
Description: | Number of treatment emergent adverse events as assessed by CTCAE v5.0 |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | ImmunoGen, Inc. |
Trial Keywords
- Antibody Drug Conjugate
- Phase 1/2
- Solid Tumors
Last Updated
June 9, 2021