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

Neoplasms Clinical Trial

Official title:

Phase 1 Study of Anti-TGFβRII Monoclonal Antibody IMC-TR1 (LY3022859) in Patients With Advanced Solid Tumors That Have Failed Standard Therapy or for Which No Standard is Available

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01646203
• Other study ID #: 14549
• Secondary ID: I5I-IE-JTCA
• Status: Completed
• Phase: Phase 1
• Start date: July 2012
• Est. completion date: October 2014

Study information

• Verified date: August 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (TGFß) 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

Related Conditions & MeSH terms

• Neoplasms
• Tumor

Intervention

Biological:
• IMC-TR1
Administered intravenously

Locations

Country	Name	City	State
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Houston	Texas
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Nashville	Tennessee
United States	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose-Limiting Toxicities (DLTs)	A DLT was defined as an AE occurring during Cycle 1(first 6 weeks of treatment) that was considered at least possibly related to study drug, was considered dose-dependent, and fulfilled a criteria selected (using the National Cancer Institute Common Terminology Criteria for Adverse Events,version 4.0 [NCI-CTCAE v 4.0] [NCI 2009]):Grade(Gr)=3 nonhematological toxicity,Gr4 thrombocytopenia lasting at least 5 days and/or complicated with bleeding,Gr=3 febrile neutropenia(ntr),Gr4 ntr of >5 days' duration,increase(incr)of at least 1 gr from a preexisting Gr1 valvular insufficiency or any new Gr=2 valvular toxicity,left ventricular(vtr) ejection fraction decrease of 10% in absolute value or 16% in relative value,incr in right vtr systolic pressure dysfunction from mild to moderate(mod) or from mod to severe,incr in left atrial or ventricular chamber size of =2 cm and =1cm respectively,any other life-threatening toxicity,significant morphologic on cardiac echocardiogram,any major ocular.	First Dose Up to 6 Weeks
Secondary	Maximum Tolerated Dose (MTD) of IMC-TR1	The MTD was defined as the highest dose level at which =33% of participants experienced a DLT during Cycle 1.	First Dose through Cycle 1 (6 Weeks)
Secondary	Maximum Tolerated Dose (MTD) of IMC-TR1 (1.25 mg/kg LY3022859 ) for Participants Receiving a Weight-Based Dose	The MTD was defined as the highest dose level at which =33% of participants experienced a DLT during Cycle 1.	First Dose through Cycle 1 (6 Weeks)
Secondary	Number of Dose-Limiting Toxicities (DLTs)		First Dose through Cycle 1 (6 Weeks)
Secondary	Immunogenicity - Development of Antibodies Against IMC-TR1		Cycle 1 - Day 1 and Day 29, Cycle 2 - Day 15, Cycle 3 and Each Consecutive Cycle - Day 1
Secondary	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) (Antitumor Activity of IMC-TR1 as Monotherapy, Assessed Via Tumor Measurement by Response Evaluation Criteria in Solid Tumors, Version 1.1)	ORR is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.	First Dose to Measured Progressive Disease (Up To 21.3 Weeks)
Secondary	Pharmacokinetics (PK) - Area Under the Concentration-time Curve (AUC[0-tlast]) and AUCt of IMC-TR1	AUC (0-tlast) is area under the concentration versus time curve from the time zero to tlast.; AUCt is area under the concentration versus time curve during 1 dose interval (336 hours).	Cycle (C) 1 Day (D) 1: 1, 2, 4, 8 hours (h); C1 D2: 24 h; C1 D3: 48 h; C1 D5: 96 h; C1 D8: 168 h; C1 D15: 336 h; C2 D15: 1, 2, 4, 8 h; C2 D16: 24 h; C2 D17: 48 h; C2 D19: 96 h; C2 D22: 168 h, C2 D29: 336 h
Secondary	Pharmacokinetics - Maximum Concentration (Cmax) of IMC-TR1		Cycle (C) 1 Day (D) 1: 1, 2, 4, 8 hours (h); C1 D2: 24 h; C1 D3: 48 h; C1 D5: 96 h; C1 D8: 168 h; C1 D15: 336 h; C2 D15: 1, 2, 4, 8 h; C2 D16: 24 h; C2 D17: 48 h; C2 D19: 96 h; C2 D22: 168 h, C2 D29: 336 h
Secondary	Pharmacokinetics - Minimum Concentration (Cmin) of IMC-TR1	Pharmacokinetics - Minimum concentration (Cmin) of IMC-TR1	Cycle 2 Day 1: Prior to fourth infusion 0 hour (h)