Clinical trial NCT01646203: A Study of IMC-TR1 in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Tumor
Keywords: Advanced Solid Tumors
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-07-20
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: First Dose Up to 6 Weeks
Secondary outcomes:
measure: Maximum Tolerated Dose (MTD) of IMC-TR1
timeFrame: First Dose through Cycle 1 (6 Weeks)
measure: Maximum Tolerated Dose (MTD) of IMC-TR1 (1.25 mg/kg LY3022859 ) for Participants Receiving a Weight-Based Dose
timeFrame: First Dose through Cycle 1 (6 Weeks)
measure: Number of Dose-Limiting Toxicities (DLTs)
timeFrame: First Dose through Cycle 1 (6 Weeks)
measure: Immunogenicity - Development of Antibodies Against IMC-TR1
timeFrame: Cycle 1 - Day 1 and Day 29, Cycle 2 - Day 15, Cycle 3 and Each Consecutive Cycle - Day 1
measure: 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)
timeFrame: First Dose to Measured Progressive Disease (Up To 21.3 Weeks)
measure: Pharmacokinetics (PK) - Area Under the Concentration-time Curve (AUC[0-tlast]) and AUCτ of IMC-TR1
timeFrame: 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
measure: Pharmacokinetics - Maximum Concentration (Cmax) of IMC-TR1
timeFrame: 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
measure: Pharmacokinetics - Minimum Concentration (Cmin) of IMC-TR1
timeFrame: Cycle 2 Day 1: Prior to fourth infusion 0 hour (h)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: 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
state: Tennessee
city: Houston
country: United States
facility: 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
state: Texas
city: San Antonio
country: United States
facility: 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
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Tolcher AW, Berlin JD, Cosaert J, Kauh J, Chan E, Piha-Paul SA, Amaya A, Tang S, Driscoll K, Kimbung R, Kambhampati SR, Gueorguieva I, Hong DS. A phase 1 study of anti-TGFbeta receptor type-II monoclonal antibody LY3022859 in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2017 Apr;79(4):673-680. doi: 10.1007/s00280-017-3245-5. Epub 2017 Mar 9.