A Study of IMC-TR1 in Participants With Advanced Solid Tumors

Lilly

Status and phase: Completed; Phase 1

Conditions: Neoplasms; Tumor

Treatments: Biological: IMC-TR1

Study type: Interventional

Funder types: Industry

Identifiers

NCT01646203

I5I-IE-JTCA (Other Identifier)

14549

Details and patient eligibility

About

A study to evaluate the safety and tolerability of anti-TGFβRII monoclonal antibody (IMC-TR1) in participants with advanced solid tumors, as well as gather evidence of anti-tumor activity.

Full description

This is the first-in-human Phase 1 study of IMC-TR1.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Part A and Part B: Participants must be appropriate candidates for experimental therapy, with a solid tumor that has failed standard therapy or for which no standard therapy is available, and evidence of progressive disease

  • Part A only: Participants must have histological or cytological evidence of a solid tumor which is advanced and/or metastatic
  • Part B only: Participants who have failed first-line therapy/standard of care and have histological or cytological evidence of a cancer type for which evidence of activity was observed during Part A or for which preclinical evidence of potential activity has been observed

• Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

  • Part A only: Participants may have measurable or nonmeasurable disease
  • Part B: Participants must have measurable disease

• Have adequate organ function including: Hematologic, Hepatic, Albumin, Coagulation and Renal function

• Have a performance status of ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have discontinued previous treatments for cancer and recovered from the acute effects of therapy

• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug

• Females with child bearing potential must have had a negative serum pregnancy test and must not be breastfeeding

• Have an estimated life expectancy that is > 3 months

Exclusion criteria

• Have clinically significant cardiac disease, including:

  • Myocardial infarction within 6 months prior to study entry, unstable angina pectoris, congestive heart failure, or uncontrolled hypertension
  • Major electrocardiogram (ECG) abnormalities
  • Major abnormalities documented by echocardiography with Doppler
  • Have known predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress
  • Have Corrected QT Interval (QTc interval) of > 500 msec on screening ECG

• Have other known serious pre-existing medical conditions

• Have received prior investigational therapy targeting Transforming growth factor beta (TGFβ) or its receptors

• Have a known sensitivity to monoclonal antibodies or other therapeutic proteins, to agents of similar biologic composition as IMC-TR1

• Have a high risk of gastrointestinal bleeding, active inflammatory bowel disease, or chronic steroid use

• Are currently using or has received a systemic thrombolytic agent within 28 days prior to enrollment

• Are receiving:

  • full-dose warfarin
  • intravenous heparin or low-molecular-weight heparin
  • chronic daily treatment with aspirin at a dose greater than 325 mg per day or nonsteroidal anti-inflammatory medications known to inhibit platelet function

• Have evidence of retinal disease or are a monocular participant

• Have received a solid organ transplant, bone marrow transplant or stem cell transplant

• Have symptomatic central nervous system (CNS) malignancy or untreated metastasis

• Have acute or chronic leukemia

• Have a known active fungal, bacterial, and/or viral infection including human immunodeficiency virus or viral hepatitis requiring treatment

• Has a positive fecal occult blood test within 14 days prior to enrollment

Trial design

14 participants in 1 patient group

IMC-TR1

Experimental group

Description:

Part A - Dose Escalation: Cohort 1A: 1.25 mg/kg, intravenously (IV), every 2 weeks of the 6-week treatment cycle Cohorts 1B-9: Dose Escalation from 12.5 mg to 1600 mg (flat dose), intravenously (IV), every 2 weeks of the 6-week treatment cycles Cohorts 10-12: Dose escalation from 800 mg to 1600 mg (flat dose), intravenously (IV), weekly during the 6-week treatment cycles Part B - Disease Specific Cohort Expansion: Participants will be enrolled into each of three tumor-specific cohort expansions. Participants will be treated with recommended Phase 2 dose.

Treatment:

Biological: IMC-TR1