Advanced Solid TumorPhase 1/2NCT04622774
First-in-Human Study of IMGC936 in Participants With Advanced Solid Tumors
A Phase 1/2 study testing IMGC936 in people with Advanced Solid Tumor, run by ImmunoGen, Inc. at 13 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- IMGC936
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 13 sitesin 3 countries
- Study dates
- 29 Oct 2020to 28 Dec 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants with histologically proven, relapsed or refractory, unresectable locally advanced or metastatic non-squamous NSCLC, TNBC, CRC, gastroesophageal cancer, or pancreatic cancer for whom no therapy with demonstrated clinical benefit is available.
- NSCLC: Participants must have been treated with 1 to 4 prior lines of systemic therapy with no more than 2 chemotherapy containing lines.
- TNBC: Participants must have been treated with 1 to 4 prior lines of systemic therapy for metastatic disease, excluding adjuvant therapies.
- CRC: Participants must have been treated with 1 to 3 prior lines of systemic therapy.
- Gastroesophageal cancer: Participants must have been treated with 1 to 3 prior lines of systemic therapy.
- Pancreatic cancer: Participants must have been treated with 1 to 3 prior lines of systemic therapy, with no more than 2 chemotherapy containing lines.
Show all 24Show fewer
- Either measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI) obtained within 28 days of Cycle 1 Day 1 (C1D1).
- Dose escalation: Participants may have non-measurable or measurable disease
- Dose expansion: Participants must have measurable disease
- Age ≥ 18 years old.
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. If ECOG performance status is an inappropriate performance measurement for participant enrollment (for example, chronically non-ambulatory), then Karnofsky performance status must be ≥ 70.
- Life expectancy ≥ 12 weeks.
- Acceptable laboratory parameters as follows:
- Platelet count ≥ 75 × 1000/microliter (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) >30 milliliters (mL)/ minute (min)/1.73 square meter (m^2) 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).
- 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.
- 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.
- 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.
Who cannot join
- Active central nervous system (CNS) disease within the last 6 months.
- 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.
- 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.
- Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia).
Show all 29Show fewer
- 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, for example, atrial fibrillation that are not well controlled with optimal medical intervention.
- Current uncontrolled hypertension: systolic blood pressure > 160 millimeters of mercury (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 milliseconds (msec)
- 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.
- 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.
- History of prior bone marrow, stem cell, or solid organ transplantation.
- 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.
- Major trauma or major surgery within 4 weeks prior to initiation of study drug.
- 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.
- Known hypersensitivity to any ingredient or any excipient contained in the drug formulation
- Vaccination with any live virus vaccine within 4 weeks prior to initiation of study drug. Inactivated annual influenza vaccination is allowed.
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
United States7 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Sarah Cannon Research Institute
Denver, Colorado, 80218
MD Anderson Cancer Center
Houston, Texas, 77030
UCSD
La Jolla, California, 92037
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Florida Cancer Specialists
Sarasota, Florida, 34232
Washington University
St Louis, Missouri, 63110
Italy3 sites
Policlinico di Modena
Modena, 41124
IRCCS Humanitas
Rozzano, 20089
Azienda Ospedaliera Universitaria Senese
Siena, 53100
Spain3 sites
START Madrid-FJD Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
START Madrid-HM CIOCC
Madrid, 28050
Hospital Universitario Quirónsalud Madrid
Madrid, 28223
About this study
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
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.
Read the 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 (RP2D). 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 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 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.
- Conditions
- Advanced Solid Tumor
- Being tested
- IMGC936
- Keywords
- Antibody Drug Conjugate, Phase 1/2, Solid Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMGC936Drug
Antibody Drug Conjugate
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation - Schedule A: IMGC936 0.5 mg/kg | Experimental | Participants received IMGC936 0.5 milligrams (mg)/kilogram (kg) via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
| Dose Escalation - Schedule A: IMGC936 1.0 mg/kg | Experimental | Participants received IMGC936 1.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
| Dose Escalation - Schedule A: IMGC936 2.0 mg/kg | Experimental | Participants received IMGC936 2.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
| Dose Escalation - Schedule A: IMGC936 4.0 mg/kg | Experimental | Participants received IMGC936 4.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
| Dose Escalation - Schedule A: IMGC936 5.0 mg/kg | Experimental | Participants received IMGC936 5.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
| Dose Escalation - Schedule A: IMGC936 6.0 mg/kg | Experimental | Participants received IMGC936 6.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
| Dose Escalation - Schedule A: IMGC936 7.0 mg/kg | Experimental | Participants received IMGC936 7.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
| Dose Escalation - Schedule B: IMGC936 2.0 mg/kg | Experimental | Participants received IMGC936 2.0 mg/kg on Days 1, 8, and 15 of a 28-day cycle for the first 2 cycles. On all subsequent cycles (Cycle 3 and beyond), participants received IMGC936 2.0 mg/kg on Days 1 and 8 of a 28-day cycle. Receives: Drug: IMGC936 |
| Dose Expansion - NSCLC: IMGC936 6.0 mg/kg | Experimental | Participants received IMGC936 6.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
| Dose Expansion - TNBC: IMGC936 6.0 mg/kg | Experimental | Participants received IMGC936 6.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. Receives: Drug: IMGC936 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as any AEs with onset date between the first dose of IMGC936 and date of the last dose of IMGC936 + 30 days (inclusive) or date of the first anti-cancer therapy, whichever was earlier. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: Up to approximately 3 years
Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for AEs Version 5.0 (CTCAE v5.0)
DLTs were defined based on TEAEs or abnormal laboratory values that met DLT criteria. Hematologic DLT: Grade 4 neutropenia lasting >7 days; ≥Grade 3 febrile neutropenia Grade 4 thrombocytopenia; Grade 3 thrombocytopenia associated with bleeding; ≥Grade 3 hemolysis. Non-hematologic DLT: Any ≥Grade 3 non-hematologic event, including Grade 3 ocular symptoms and signs; Grade 2 AEs that were prolonged inordinately; • Hepatic laboratory abnormalities meeting Hy's law criteria; Eye pain or reduction in visual acuity that did not respond to topical ophthalmic therapy. Hepatic DLT: Any elevation of ≥1 transaminases >8 * upper limit of normal (ULN); Any Grade 3 elevation of ≥1 transaminases >5.0-8.0 * ULN that did not resolve to Grade 2 within 7 days and Grade 1 within 14 days; Grade 3 elevation of total bilirubin >5 * ULN; Any Grade 3 elevation of total bilirubin >3.0-5.0 * ULN that did not resolve to Grade 2 within 7 days and Grade 1 within 14 days; Any event meeting criteria for Hy's law.
Measured: Cycle 1 (21 days for Schedule A and 28 days for Schedule B)
Dose Expansion Phase: Objective Response Rate (ORR) - Percentage of Participants With Objective Response as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
ORR was defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm). PR: At least 30% decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
Measured: Up to approximately 3 years
Secondary outcomes (6)
Dose Escalation and Dose Expansion Phase: Maximum Study Drug Concentration (Cmax)
Measured: Schedule A: Cycle 1 Day 1 (C1D1), C3D1; Schedule B: C1D1, C1D15
Dose Escalation and Dose Expansion Phase: Number of Participants With Antidrug Antibodies (ADA)
Measured: Up to approximately 3 years
Dose Escalation Phase: ORR - Percentage of Participants With Objective Response as Assessed by the Investigator Using RECIST v1.1
ORR was defined as percentage of participants with a confirmed BOR of CR or PR. CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least 30% decrease in the SoD of target lesions, taking as reference the baseline SoD.
Measured: Up to approximately 3 years
Dose Escalation and Dose Expansion Phase: Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
DOR was defined as the time from the date of the first response (CR or PR), until the date of progressive disease (PD) or death from any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was estimated using the Kaplan-Meier method.
Measured: Up to approximately 3 years
Dose Expansion Phase: Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1
PFS was defined as the time from initiation of study drug until the date of PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Measured: Up to approximately 3 years
Dose Expansion Phase: Number of Participants With TEAEs, SAEs, and IMGC936 Related TEAEs That Led to Discontinuation
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as any AEs with onset date between the first dose of IMGC936 and date of the last dose of IMGC936 + 30 days (inclusive) or date of the first anti-cancer therapy, whichever was earlier. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: Up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2020
- Study start29 Oct 2020
- Primary completion28 Dec 2023
- Study completion28 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- ImmunoGen, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- MacroGenics
- Responsible party
- Sponsor
- Investigators
- CMO ImmunoGen, Study director, ImmunoGen, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04622774
- Sponsor's protocol ID
- IMGC936-0901
- Status last verified
- Dec 2024
- First submitted
- 27 Oct 2020
- Last updated
- 15 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Park EJ, Lee CW. Soluble receptors in cancer: mechanisms, clinical significance, and therapeutic strategies. Exp Mol Med. 2024 Feb;56(1):100-109. doi: 10.1038/s12276-023-01150-6. Epub 2024 Jan 5.
PubMed 38182653Scribner JA, Hicks SW, Sinkevicius KW, Yoder NC, Diedrich G, Brown JG, Lucas J, Fuller ME, Son T, Dastur A, Hooley J, Espelin C, Themeles M, Chen FZ, Li Y, Chiechi M, Lee J, Barat B, Widjaja L, Gorlatov S, Tamura J, Ciccarone V, Ab O, McEachem KA, Koenig S, Westin EH, Moore PA, Chittenden T, Gregory RJ, Bonvini E, Loo D. Preclinical Evaluation of IMGC936, a Next-Generation Maytansinoid-based Antibody-drug Conjugate Targeting ADAM9-expressing Tumors. Mol Cancer Ther. 2022 Jul 5;21(7):1047-1059. doi: 10.1158/1535-7163.MCT-21-0915.
PubMed 35511740
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04622774
- Acronym / sponsor ID
- IMGC936-0901
- Conditions
- Advanced Solid Tumor
- Keywords
- Antibody Drug Conjugate, Phase 1/2, Solid Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- ImmunoGen, Inc.Industry (pharma, biotech, devices)
- Collaborators
- MacroGenics
- Study start
- 29 Oct 2020 (actual)
- Primary completion
- 28 Dec 2023 (actual)
- Study completion
- 28 Dec 2023 (actual)
- First posted
- 10 Nov 2020 (actual)
- Results
- Posted 15 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (RP2D). 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 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation - Schedule A: IMGC936 0.5 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 0.5 milligrams (mg)/kilogram (kg) via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
| Dose Escalation - Schedule A: IMGC936 1.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 1.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
| Dose Escalation - Schedule A: IMGC936 2.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 2.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
| Dose Escalation - Schedule A: IMGC936 4.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 4.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
| Dose Escalation - Schedule A: IMGC936 5.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 5.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
| Dose Escalation - Schedule A: IMGC936 6.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 6.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
| Dose Escalation - Schedule A: IMGC936 7.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 7.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
| Dose Escalation - Schedule B: IMGC936 2.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 2.0 mg/kg on Days 1, 8, and 15 of a 28-day cycle for the first 2 cycles. On all subsequent cycles (Cycle 3 and beyond), participants received IMGC936 2.0 mg/kg on Days 1 and 8 of a 28-day cycle. |
| Dose Expansion - NSCLC: IMGC936 6.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 6.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
| Dose Expansion - TNBC: IMGC936 6.0 mg/kg | Experimental | Drug: IMGC936Participants received IMGC936 6.0 mg/kg via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Participants with histologically proven, relapsed or refractory, unresectable locally advanced or metastatic non-squamous NSCLC, TNBC, CRC, gastroesophageal cancer, or pancreatic cancer for whom no therapy with demonstrated clinical benefit is available.
- Either measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI) obtained within 28 days of Cycle 1 Day 1 (C1D1).
- Age ≥ 18 years old.
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. If ECOG performance status is an inappropriate performance measurement for participant enrollment (for example, chronically non-ambulatory), then Karnofsky performance status must be ≥ 70.
Key exclusion criteria (29 listed)
- Active central nervous system (CNS) disease within the last 6 months.
- 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.
- Participants who had prior therapies within the specified times below:
- Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia).
- Clinically significant cardiovascular disease including but not limited to:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMGC936Antibody Drug Conjugate | Drug | Dose Escalation - Schedule A: IMGC936 0.5 mg/kg, Dose Escalation - Schedule A: IMGC936 1.0 mg/kg, Dose Escalation - Schedule A: IMGC936 2.0 mg/kg, Dose Escalation - Schedule A: IMGC936 4.0 mg/kg, Dose Escalation - Schedule A: IMGC936 5.0 mg/kg, Dose Escalation - Schedule A: IMGC936 6.0 mg/kg, Dose Escalation - Schedule A: IMGC936 7.0 mg/kg, Dose Escalation - Schedule B: IMGC936 2.0 mg/kg, Dose Expansion - NSCLC: IMGC936 6.0 mg/kg, Dose Expansion - TNBC: IMGC936 6.0 mg/kg |
Primary outcome
Dose Escalation Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to approximately 3 years
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as any AEs with onset date between the first dose of IMGC936 and date of the last dose of IMGC936 + 30 days (inclusive) or date of the first anti-cancer therapy, whichever was earlier. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for AEs Version 5.0 (CTCAE v5.0)
Time frame: Cycle 1 (21 days for Schedule A and 28 days for Schedule B)
DLTs were defined based on TEAEs or abnormal laboratory values that met DLT criteria. Hematologic DLT: Grade 4 neutropenia lasting >7 days; ≥Grade 3 febrile neutropenia Grade 4 thrombocytopenia; Grade 3 thrombocytopenia associated with bleeding; ≥Grade 3 hemolysis. Non-hematologic DLT: Any ≥Grade 3 non-hematologic event, including Grade 3 ocular symptoms and signs; Grade 2 AEs that were prolonged inordinately; • Hepatic laboratory abnormalities meeting Hy's law criteria; Eye pain or reduction in visual acuity that did not respond to topical ophthalmic therapy. Hepatic DLT: Any elevation of ≥1 transaminases >8 * upper limit of normal (ULN); Any Grade 3 elevation of ≥1 transaminases >5.0-8.0 * ULN that did not resolve to Grade 2 within 7 days and Grade 1 within 14 days; Grade 3 elevation of total bilirubin >5 * ULN; Any Grade 3 elevation of total bilirubin >3.0-5.0 * ULN that did not resolve to Grade 2 within 7 days and Grade 1 within 14 days; Any event meeting criteria for Hy's law.
Dose Expansion Phase: Objective Response Rate (ORR) - Percentage of Participants With Objective Response as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: Up to approximately 3 years
ORR was defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm). PR: At least 30% decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
6 secondary outcomes
Dose Escalation and Dose Expansion Phase: Maximum Study Drug Concentration (Cmax)
Time frame: Schedule A: Cycle 1 Day 1 (C1D1), C3D1; Schedule B: C1D1, C1D15
Dose Escalation and Dose Expansion Phase: Number of Participants With Antidrug Antibodies (ADA)
Time frame: Up to approximately 3 years
Dose Escalation Phase: ORR - Percentage of Participants With Objective Response as Assessed by the Investigator Using RECIST v1.1
Time frame: Up to approximately 3 years
Dose Escalation and Dose Expansion Phase: Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
Time frame: Up to approximately 3 years
Dose Expansion Phase: Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1
Time frame: Up to approximately 3 years
Dose Expansion Phase: Number of Participants With TEAEs, SAEs, and IMGC936 Related TEAEs That Led to Discontinuation
Time frame: Up to approximately 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38182653Park EJ, Lee CW. Soluble receptors in cancer: mechanisms, clinical significance, and therapeutic strategies. Exp Mol Med. 2024 Feb;56(1):100-109. doi: 10.1038/s12276-023-01150-6. Epub 2024 Jan 5.
- Derived from this study: PubMed 35511740Scribner JA, Hicks SW, Sinkevicius KW, Yoder NC, Diedrich G, Brown JG, Lucas J, Fuller ME, Son T, Dastur A, Hooley J, Espelin C, Themeles M, Chen FZ, Li Y, Chiechi M, Lee J, Barat B, Widjaja L, Gorlatov S, Tamura J, Ciccarone V, Ab O, McEachem KA, Koenig S, Westin EH, Moore PA, Chittenden T, Gregory RJ, Bonvini E, Loo D. Preclinical Evaluation of IMGC936, a Next-Generation Maytansinoid-based Antibody-drug Conjugate Targeting ADAM9-expressing Tumors. Mol Cancer Ther. 2022 Jul 5;21(7):1047-1059. doi: 10.1158/1535-7163.MCT-21-0915.
Related trials for Advanced Solid Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
CMO ImmunoGen study director
ImmunoGen, Inc.
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IMGC936 in people with Advanced Solid Tumor, run by ImmunoGen, Inc. at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Up to approximately 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04622774, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2025.