First-in-Human Study of IMGC936 in Participants With Advanced Solid Tumors

NCT04622774 | Completed Phase 1 Results FDA Drug

• 1 other identifier: IMGC936-0901
• Study Type: interventional
• Target: 56
• Locations: 3 countries
• Sites: 13

Brief 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.

Conditions

Advanced Solid Tumor

Keywords

Antibody Drug Conjugate; Phase 1/2; Solid Tumors

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to approximately 3 years

Secondary Outcomes (6)

• Dose Escalation and Dose Expansion Phase: Maximum Study Drug Concentration (Cmax)

  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)

  Up to approximately 3 years

• Dose Escalation Phase: ORR - Percentage of Participants With Objective Response as Assessed by the Investigator Using RECIST v1.1

  Up to approximately 3 years

• Dose Escalation and Dose Expansion Phase: Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1

  Up to approximately 3 years

• Dose Expansion Phase: Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1

  Up to approximately 3 years

Study Arms (10)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Drug: IMGC936

Interventions

IMGC936 DRUG

Antibody Drug Conjugate

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• ImmunoGen, Inc.: lead
• MacroGenics: collaborator

Study Sites (13)

UCSD

La Jolla, California, 92037, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Policlinico di Modena

Modena, 41124, Italy

Location

IRCCS Humanitas

Rozzano, 20089, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

START Madrid-FJD Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

START Madrid-HM CIOCC

Madrid, 28050, Spain

Location

Hospital Universitario Quirónsalud Madrid

Madrid, 28223, Spain

Location

Related Publications (1)

• Scribner 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.

  PMID: 35511740 DERIVED

Results Point of Contact

• Title: CMO, ImmunoGen
• Organization: ImmunoGen, Inc

clinicaltrials@immunogen.com

781-895-0600

Study Officials

• CMO ImmunoGen

  ImmunoGen, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: November 10, 2020
• Study Start: October 29, 2020
• Primary Completion: December 28, 2023
• Study Completion: December 28, 2023
• Last Updated: January 15, 2025
• Results First Posted: January 15, 2025

Record last verified: 2024-12

Locations

US (7); ES (3); IT (3)