Solid TumorPhase 1NCT03752177
A Study of LY3415244 in Participants With Advanced Solid Tumors
A Phase 1 study testing LY3415244 in people with Solid Tumor, run by Eli Lilly and Company at 6 sites in 3 countries.
Trial summary
The goal of this study is to evaluate the safety of LY3415244, a PD-L1/TIM-3 bispecific antibody, administered as monotherapy to participants with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- LY3415244
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 22 Nov 2018to 9 Oct 2019
- 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
- For Phase 1a/b, histologic or cytologic confirmation of advanced solid tumor.
- For Phase 1a/b, biopsy of tumor samples are required. Newly obtained core or excisional biopsy of a tumor lesion prior to study enrollment and undergo a biopsy procedure during the study.
- Phase 1a, prior anti-PD-1 or anti-PD-L1 therapy or other immunotherapy is allowed.
- Phase 1b, prior anti-PD-1 or anti-PD-L1 therapy is required where anti-PD-1 or anti-PD-L1 is standard of care in respective tumor types if the following criteria are met:
- Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
- Must have completely recovered to baseline level prior to screening from any adverse events (AEs) that occurred from receiving prior immunotherapy
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- Must not have experienced a Grade ≥3 immune-related AE or immune related neurologic or ocular AE, pneumonitis or cardiomyopathy of any grade while receiving prior immunotherapy
- Must not have required immunosuppressive agent, other than corticosteroids for the management of an adverse event and not currently require maintenance doses of >10 milligrams (mg) prednisone (or equivalent) per day
- Must have at least 1 measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- Have adequate organ function.
- Have an estimated life expectancy ≥12 weeks, in the judgement of the investigator.
Who cannot join
- Have symptomatic central nervous system (CNS) malignancy or metastasis not requiring concurrent treatment, including but not limited to surgery, radiation, corticosteroids and/or anticonvulsants to treat CNS metastases, and their disease is asymptomatic and radiographically stable for at least 30 days.
- Have received a live vaccine within 30 days before the first dose of study treatment.
- If female, is pregnant, breastfeeding, or planning to become pregnant.
- Have a history or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the participant's participation.
- Have moderate or severe cardiovascular disease.
- Have a serious concomitant systemic disorder that would compromise the participant's ability to adhere to the protocol, including known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment.
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- Use of escalating or chronic supraphysiologic doses of corticosteroids or immunosuppressive agents (such as, cyclosporine). [Use of topical, ophthalmic, inhaled, and intranasal corticosteroids permitted].
- Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
- Evidence of interstitial lung disease or noninfectious pneumonitis.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States2 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Belgium2 sites
Institut Jules Bordet
Brussels, 1000
Universitair Ziekenhuis Gent
Ghent, 9000
Japan2 sites
National Cancer Center Hospital
Chuo-Ku, Tokyo, 104-0045
National Cancer Center Hospital East
Kashiwa, Chiba, 277 8577
About this study
Official title: A Phase 1a/1b Study of LY3415244, a Bispecific Antibody in Patients With Advanced Solid Tumors
The goal of this study is to evaluate the safety of LY3415244, a PD-L1/TIM-3 bispecific antibody, administered as monotherapy to participants with advanced solid tumors.
- Conditions
- Solid Tumor
- Being tested
- LY3415244
- Keywords
- TIM-3, PD-L1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3415244Drug
Administered IV
| Study group | Role | What they receive |
|---|---|---|
| LY3415244 Dose Escalation | Experimental | Participants received 3 milligrams (mg) LY3415244 (Cohort A1), 10 mg LY3415244 (Cohort A2), 30 mg LY3415244 (Cohort A3) and 70 mg LY3415244 (Cohort A4) as an intravenous (IV) infusion on day (D)1 and D15 of each 28-day cycle every 2 weeks (Q2W). Receives: Drug: LY3415244 |
| LY3415244 Dose Expansion | Experimental | Phase 1b dose expansion was planned but not initiated as dose escalation ended at cohort A4. Study did not achieve its primary objective of establishing a recommended phase 2 dose (RP2D) due to early termination of the study by Cohort A4. Receives: Drug: LY3415244 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)
A DLT was defined as an adverse event (AE) occurring during Cycle 1(28 days) 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 3 thrombocytopenia requiring platelet transfusion or grade 4 thrombocytopenia. Grade greater than or equal to (≥) 3 febrile neutropenia, anemia requiring a blood transfusion and any other Grade 4 hematologic toxicity that last >7 days. Grade ≥ 3 colitis or noninfectious pneumonitis, Grade ≥ 3 fatigue lasting >7 days, Grade ≥ 3 hypertension despite of maximal medical therapy. Grade 4 immune-related adverse event (irAE), liver transaminase elevation >8x upper limit of normal (ULN) or total bilirubin >3x ULN.
Measured: Baseline through Cycle 1 (28 Day Cycle)
Secondary outcomes (6)
Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244
Cmin of LY3415244 was evaluated.
Measured: Cycle 1 Day 1 (C1D1) and C1D15: pre-dose, 2 hours(h), 4h, 24h, 72h, 120h and 168h post-dose; C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C5D15, C6D1 and C6D15: pre-dose
Phase1b: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Measured: Baseline through Measured Progressive Disease (Up To 24 Months)
Phase1b: Duration of Response (DoR)
Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.
Measured: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)
Phase1b: Time to Response (TTR)
Data were not captured as study was terminated early and no participant were enrolled into Phase 1b expansion. Time to treatment response was defined as date of first dose of study drug to the date of confirmed complete response (CR) or partial response (PR) using Response evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Measured: Baseline to Date of CR or PR (Up To 24 Months)
Phase1b: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease
DCR is the percentage of participants with a best overall response of CR, PR or stable disease (SD) as defined by RECIST v1.1. CR is defined as disappearance of all target and non-target lesions and no appearance of new lesions.PR is defined as at least a 30% decrease in sum of longest diameter (LD) of target lesions (taking as reference the baseline sum LD),no progression of non-target lesions, and no appearance of new lesions.SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.
Measured: Baseline through Measured Progressive Disease (Up To 24 Months)
Phase1b: Progression Free Survival (PFS)
Progression-free survival time was measured from treatment start until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Patients who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of treatment start if no post-baseline radiographic assessment is available.
Measured: Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2018
- Study start22 Nov 2018
- Primary completion9 Oct 2019
- Study completion9 Oct 2019
Why it stopped: The study was terminated during dose escalation after a determination was made that the risk:benefit ratio no longer favored continued evaluation.
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.
- Other trials for Solid TumorStudies 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
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 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
- NCT03752177
- Sponsor's protocol ID
- 17099
- Other IDs
- J1C-MC-JZDA, 2018-001598-25, 2018
- Status last verified
- Oct 2021
- First submitted
- 16 Nov 2018
- Last updated
- 22 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1a/1b Study of LY3415244, a Bispecific Antibody in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03752177
- Acronym / sponsor ID
- 17099
- Conditions
- Solid Tumor
- Keywords
- TIM-3, PD-L1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated during dose escalation after a determination was made that the risk:benefit ratio no longer favored continued evaluation.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 22 Nov 2018 (actual)
- Primary completion
- 9 Oct 2019 (actual)
- Study completion
- 9 Oct 2019 (actual)
- First posted
- 23 Nov 2018 (actual)
- Results
- Posted 31 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to evaluate the safety of LY3415244, a PD-L1/TIM-3 bispecific antibody, administered as monotherapy to participants with advanced solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LY3415244 Dose Escalation | Experimental | Drug: LY3415244Participants received 3 milligrams (mg) LY3415244 (Cohort A1), 10 mg LY3415244 (Cohort A2), 30 mg LY3415244 (Cohort A3) and 70 mg LY3415244 (Cohort A4) as an intravenous (IV) infusion on day (D)1 and D15 of each 28-day cycle every 2 weeks (Q2W). |
| LY3415244 Dose Expansion | Experimental | Drug: LY3415244Phase 1b dose expansion was planned but not initiated as dose escalation ended at cohort A4. Study did not achieve its primary objective of establishing a recommended phase 2 dose (RP2D) due to early termination of the study by Cohort A4. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- For Phase 1a/b, histologic or cytologic confirmation of advanced solid tumor.
- For Phase 1a/b, biopsy of tumor samples are required. Newly obtained core or excisional biopsy of a tumor lesion prior to study enrollment and undergo a biopsy procedure during the study.
- Phase 1a, prior anti-PD-1 or anti-PD-L1 therapy or other immunotherapy is allowed.
- Phase 1b, prior anti-PD-1 or anti-PD-L1 therapy is required where anti-PD-1 or anti-PD-L1 is standard of care in respective tumor types if the following criteria are met:
- Must have at least 1 measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Key exclusion criteria (9 listed)
- Have symptomatic central nervous system (CNS) malignancy or metastasis not requiring concurrent treatment, including but not limited to surgery, radiation, corticosteroids and/or anticonvulsants to treat CNS metastases, and their disease is asymptomatic and radiographically stable for at least 30 days.
- Have received a live vaccine within 30 days before the first dose of study treatment.
- If female, is pregnant, breastfeeding, or planning to become pregnant.
- Have a history or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the participant's participation.
- Have moderate or severe cardiovascular disease.
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 |
|---|---|---|
| LY3415244Administered IV | Drug | LY3415244 Dose Escalation, LY3415244 Dose Expansion |
Primary outcome
Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)
Time frame: Baseline through Cycle 1 (28 Day Cycle)
A DLT was defined as an adverse event (AE) occurring during Cycle 1(28 days) 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 3 thrombocytopenia requiring platelet transfusion or grade 4 thrombocytopenia. Grade greater than or equal to (≥) 3 febrile neutropenia, anemia requiring a blood transfusion and any other Grade 4 hematologic toxicity that last >7 days. Grade ≥ 3 colitis or noninfectious pneumonitis, Grade ≥ 3 fatigue lasting >7 days, Grade ≥ 3 hypertension despite of maximal medical therapy. Grade 4 immune-related adverse event (irAE), liver transaminase elevation >8x upper limit of normal (ULN) or total bilirubin >3x ULN.
6 secondary outcomes
Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244
Time frame: Cycle 1 Day 1 (C1D1) and C1D15: pre-dose, 2 hours(h), 4h, 24h, 72h, 120h and 168h post-dose; C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C5D15, C6D1 and C6D15: pre-dose
Phase1b: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
Time frame: Baseline through Measured Progressive Disease (Up To 24 Months)
Phase1b: Duration of Response (DoR)
Time frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)
Phase1b: Time to Response (TTR)
Time frame: Baseline to Date of CR or PR (Up To 24 Months)
Phase1b: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease
Time frame: Baseline through Measured Progressive Disease (Up To 24 Months)
Phase1b: Progression Free Survival (PFS)
Time frame: Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Study of LY3415244 in Participants With Advanced Solid TumorsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY3415244 in people with Solid Tumor, run by Eli Lilly and Company at 6 sites in 3 countries.
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 11 inclusion and 9 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: stopped early, as of the sponsor's last update on 22 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Belgium, Japan. 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 31 Aug 2021). 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?
Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs) (time frame: Baseline through Cycle 1 (28 Day Cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Oct 2021.