NeoplasmsPhase 1NCT01646203
A Study of IMC-TR1 in Participants With Advanced Solid Tumors
A Phase 1 study testing IMC-TR1 in people with Neoplasms and Tumor, run by Eli Lilly and Company at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- IMC-TR1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2012to Oct 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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 locations and contacts
3 sites in 1 country.
United States3 sites
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, 77030
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, 37232
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, 78229
About this study
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
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.
Read the detailed description
This is the first-in-human Phase 1 study of IMC-TR1.
- Being tested
- IMC-TR1
- Keywords
- Advanced Solid Tumors
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMC-TR1Biological
Also called LY3022859
Administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| IMC-TR1 | Experimental | 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. Receives: Biological: IMC-TR1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: First Dose Up to 6 Weeks
Secondary outcomes (8)
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.
Measured: First Dose through Cycle 1 (6 Weeks)
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.
Measured: First Dose through Cycle 1 (6 Weeks)
Number of Dose-Limiting Toxicities (DLTs)
Measured: First Dose through Cycle 1 (6 Weeks)
Immunogenicity - Development of Antibodies Against IMC-TR1
Measured: Cycle 1 - Day 1 and Day 29, Cycle 2 - Day 15, Cycle 3 and Each Consecutive Cycle - Day 1
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.
Measured: First Dose to Measured Progressive Disease (Up To 21.3 Weeks)
Pharmacokinetics (PK) - Area Under the Concentration-time Curve (AUC[0-tlast]) and AUCτ of IMC-TR1
AUC (0-tlast) is area under the concentration versus time curve from the time zero to tlast.
AUCτ is area under the concentration versus time curve during 1 dose interval (336 hours).
Measured: 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
Pharmacokinetics - Maximum Concentration (Cmax) of IMC-TR1
Measured: 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
Pharmacokinetics - Minimum Concentration (Cmin) of IMC-TR1
Pharmacokinetics - Minimum concentration (Cmin) of IMC-TR1
Measured: Cycle 2 Day 1: Prior to fourth infusion 0 hour (h)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01646203
- Sponsor's protocol ID
- 14549
- Other IDs
- I5I-IE-JTCA
- Status last verified
- Aug 2018
- First submitted
- 11 Jun 2012
- Last updated
- 18 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28280971
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01646203
- Acronym / sponsor ID
- 14549
- Keywords
- Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 20 Jul 2012 (estimated)
- Results
- Posted 18 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IMC-TR1 | Experimental | Biological: IMC-TR1Part 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
- Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
- 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
Key exclusion criteria (21 listed)
- Have clinically significant cardiac disease, including:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMC-TR1Also: LY3022859Administered intravenously | Biological | IMC-TR1 |
Primary outcome
Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: First Dose Up to 6 Weeks
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.
8 secondary outcomes
Maximum Tolerated Dose (MTD) of IMC-TR1
Time frame: First Dose through Cycle 1 (6 Weeks)
Maximum Tolerated Dose (MTD) of IMC-TR1 (1.25 mg/kg LY3022859 ) for Participants Receiving a Weight-Based Dose
Time frame: First Dose through Cycle 1 (6 Weeks)
Number of Dose-Limiting Toxicities (DLTs)
Time frame: First Dose through Cycle 1 (6 Weeks)
Immunogenicity - Development of Antibodies Against IMC-TR1
Time frame: Cycle 1 - Day 1 and Day 29, Cycle 2 - Day 15, Cycle 3 and Each Consecutive Cycle - Day 1
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)
Time frame: First Dose to Measured Progressive Disease (Up To 21.3 Weeks)
Pharmacokinetics (PK) - Area Under the Concentration-time Curve (AUC[0-tlast]) and AUCτ of IMC-TR1
Time frame: 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
Pharmacokinetics - Maximum Concentration (Cmax) of IMC-TR1
Time frame: 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
Pharmacokinetics - Minimum Concentration (Cmin) of IMC-TR1
Time frame: Cycle 2 Day 1: Prior to fourth infusion 0 hour (h)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28280971Tolcher 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IMC-TR1 in people with Neoplasms and Tumor, run by Eli Lilly and Company at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: First Dose Up to 6 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01646203, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2019.