A Study of LY2510924 and Durvalumab in Participants With Solid Tumors

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and tolerability of chemokine (C-X-C Motif) receptor 4 (CXCR4) peptide antagonist LY2510924 and durvalumab for phase 1a and 1b in participants with advanced refractory solid tumors.

Official Title
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A Phase 1a/1b Study of CXCR4 Peptide Antagonist (LY2510924) Administered in Combination With the Anti-PD-L1 Antibody, Durvalumab (MEDI4736), in Advanced Refractory Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: LY2510924
* Drug: Durvalumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase 1a: Have histologic or cytologic confirmation of advanced solid tumor Have at least 1 measurable lesion assessable using standard techniques by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Have adequate organ function Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Have provided tissue from a newly obtained core or excisional biopsy of a tumor lesion or a recent biopsy defined by ≤3 years since last documented progression of disease Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator Exclusion Criteria: Have a serious concomitant systemic disorder including human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active HCV, active autoimmune disorder or disease requiring high dose of steroids Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection or chronic diarrhea Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis Have an active infection requiring systemic therapy Have had prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-PD-L2, or anticytotoxic T lymphocyte-associated antigen-4 antibody Moderate or severe cardiovascular disease Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment Have received a live vaccine within 30 days before the first dose of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20 mg LY2510924 + 1500 mg Durvalumab<br>20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days). | Drug: LY2510924<br>* Administered SQ<br>Drug: Durvalumab<br>* Administered IV<br>|
| Experimental: 30 mg LY2510924 + 1500 mg Durvalumab<br>30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days). | Drug: LY2510924<br>* Administered SQ<br>Drug: Durvalumab<br>* Administered IV<br>|
| Experimental: 40 mg LY2510924 + 1500 mg Durvalumab<br>40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days). | Drug: LY2510924<br>* Administered SQ<br>Drug: Durvalumab<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | DLT is defined as 1 of the following adverse events(AE) reported during the Phase 1a DLT observation period,if considered to be definitely,probably,or possibly related to either study regimen by the investigator;and fulfills any 1 of the following criterion using(NCI)CTCAE version(v)4.03:Grade4 immune-related AE,Grade4 non-laboratory AE,any CTCAE Grade ≥3 QT prolongation AE,≥Grade3 colitis or noninfectious pneumonitis irrespective of duration,Grade3 immune-related AE(excluding colitis,QT prolongation,or pneumonitis) that does not downgrade to Grade2 within 3 days after onset of event despite optimal medical management including systemic corticosteroids,or does not downgrade to ≤Grade 1 or baseline within 14 days,Grade2 pneumonitis that does not resolve to ≤Grade 1 within 3 days of the initiation of maximal supportive care,including corticosteroid therapy,Grade3 toxicity lasting an extended time despite optimal supportive care and there were also laboratory abnormalities criterion. | Cycle 1 (28 Days) | 
| Maximum Tolerated Dose (MTD) of LY2510924 | MTD was determined after the evaluation of Phase 1a portion of the trial. For Phase 1a, any DLT-equivalent toxicities observed in Cycle 2 and beyond were also be considered in dose escalation and determining MTD/recommended Phase 2 dose. See outcome measure number 1 for the DLT criterion. | Cycle 1 (28 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 When Co-Administered With Durvalumab | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 when Co-Administered with Durvalumab | Cycle 1 Day 1: Predose, 0.5, 2, 4, 6, 8, 24-30 hours; Day 15: Predose, 0.5, 2, 4, 6, 8 hours | 
| Number of Participants With Anti-Durvalumab Antibodies When Administered in Combination With LY2510924 | Number of participants with treatment-emergent positive Anti-Durvalumab antibodies was summarized by treatment group. | Predose Cycle 1 Day 1 through 90 Day Post Treatment Follow Up (Up To 12 Months) | 
| Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in sum of diameter(SOD) of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100. | Baseline through Measured Progressive Disease or Death (Up To 12 Months) | 
| Percentage of Participants With CR, PR, or Stable Disease (SD) (Disease Control Rate [DCR]) | DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in sum of diameter (SOD) of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)*100. | Baseline through Measured Progressive Disease (Up To 12 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immuno-oncology