Colorectal Cancer, Esophageal Cancer, Gastric Cancer (GC), GastroEsophageal Cancer, Pancreatic Cancer, Urothelial Cancer
Conditions
Brief summary
The study is designed to characterize safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary anti-tumor activity of MGC030. Participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors of select types. The main question the study aims to answer is: * What types of side effects will participants experience when receiving MGC030? * Can MGC030 cause cancer to shrink, remain stable, or able to control disease progression of participants with advanced solid tumors? Participants will * Undergo screening procedures to determine eligibility * Receive study treatments initially every 3 weeks. * Have blood samples taken for routine and research tests * Have other examinations to check heart and lung function, and general health status * Be asked about any side effects that may be happening or other medications you are taking. The study doctor will provide treatment for side effects, if necessary. * Have the study doctor assess your tumor status at regular intervals to determine how you are responding to treatment.
Interventions
BIOLOGICALMGC030
Antibody-drug conjugate
Sponsors
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants in dose escalation cohorts must have histologically proven unresectable, locally advanced or metastatic solid tumor limited to one of the following types: urothelial cancer, colorectal cancer (CRC), gastric or gastroesophageal junction (GEJ) cancer, esophageal cancer, or pancreatic carcinoma that is refractory to standard therapy, or for which standard therapy does not exist, has proven to be intolerable, or has been refused by the participant. * Participants in expansion cohorts must have histologically proven, unresectable, locally advanced or metastatic solid tumors * Urothelial cancer with progression following platinum-containing chemotherapy for metastatic or locally advanced/unresectable cancer, or within 12 months from completion of neo-adjuvant or adjuvant platinum-containing chemotherapy for localized muscle-invasive cancer. * Gastric/GEJ carcinoma with progression during or following at least 1 systemic therapy. * Esophageal cancer with progression during or following at least 1 systemic therapy. * CRC with progression during or following treatment with at least 2 prior lines of systemic therapy (containing a fluoropyrimidine plus a platinum analogue and/or irinotecan) for metastatic disease. * CRC harboring an activating EGFR mutation must have progressed during or following at least one EGFR targeted therapy, if available. * Participants should have received no more than 4 prior lines of systemic therapy for advanced or metastatic disease. * Pancreatic cancer with progression during or following at least 1 systemic therapy. Participants should have received no more than 2 prior lines of cytotoxic chemotherapy for advanced or metastatic disease. * Participants must have at least one lesion that meets the definition of measurable disease by RECIST v1.1. * Participants must have an available archival or formalin-fixed paraffin-embedded tumor tissue or be willing to undergo a biopsy procedure to obtain a fresh tumor sample. * Participants have acceptable physical condition and laboratory values. * Participants of childbearing potential must agree to use highly effective methods of birth control. * Participants must not be pregnant, planning to be pregnant, or breastfeeding.
Exclusion criteria
* Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures. * Active brain metastases or leptomeningeal metastases. * Prior stem cell, tissue, or solid organ transplant. * Another malignancy that required treatment within the past 2 years, with the exception of those with a negligible risk of metastasis or death such as adequately treated non-melanomatous skin cancer, localized prostate cancer (Gleason Score \< 6), or carcinoma in situ. * History of primary immunodeficiency. * Active viral, bacterial, or fungal infection * Prior treatment with Topoisomerase 1-based ADCs for cancer. * Prior treatment with major surgery, mediastinal or lung radiation, vaccination with live virus vaccines, systemic cancer treatment, chimeric antigen receptor (CAR)-T cell therapy, or experimental treatment within 4 weeks of the start of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with adverse events (AEs), serious AEs (SAEs), AEs leading to dose interruption, AEs leading to dose reduction or treatment discontinuation, does limiting toxicities and AEs of special interest. | Throughout the study, estimated duration 2 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean concentrations MGC030 antibody-drug conjugate, total antibody and unconjugated payload. | Throughout the study treatment period, up to 2 years | — |
| Number of Participants Who Develop Anti-Drug Antibodies to MGC030 | Throughout the study treatment period, up to 2 years | — |
| Objective response rate | Throughout the study treatment period, up to 2 years | The ORR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is estimated as the proportion of participants in the Response Evaluable Population who achieve Best Overall Response of Complete Response or Partial Response. |
| Duration of Response | Throughout the study treatment period, up to 2 years. | DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented progression or death from any cause, whichever occurs first. |
Contacts
CONTACTGlobal Trial Manager
STUDY_DIRECTORFrank Perabo, MD, PhD
MacroGenics
Outcome results
None listed