A Study of LY2510924 and Durvalumab in Participants With Solid Tumors

NCT02737072 | Terminated Phase 1 Results

• 2 other identifiers: 16387I2V-MC-CXAD
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Solid Tumor

Keywords

immuno-oncology

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

  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)]

  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])

  Baseline through Measured Progressive Disease (Up To 12 Months)

Study Arms (3)

20 mg LY2510924 + 1500 mg Durvalumab

EXPERIMENTAL

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; Drug: Durvalumab

30 mg LY2510924 + 1500 mg Durvalumab

EXPERIMENTAL

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; Drug: Durvalumab

40 mg LY2510924 + 1500 mg Durvalumab

EXPERIMENTAL

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; Drug: Durvalumab

Interventions

LY2510924 DRUG

Administered SQ

20 mg LY2510924 + 1500 mg Durvalumab; 30 mg LY2510924 + 1500 mg Durvalumab; 40 mg LY2510924 + 1500 mg Durvalumab

Durvalumab DRUG

Administered IV

20 mg LY2510924 + 1500 mg Durvalumab; 30 mg LY2510924 + 1500 mg Durvalumab; 40 mg LY2510924 + 1500 mg Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• AstraZeneca: collaborator

Related Links

• Click here for more information about this study: A Study of LY2510924 and Durvalumab in Participants With Solid Tumors

MeSH Terms

Interventions

LY2510924; durvalumab

Limitations and Caveats

The study was terminated after the Phase 1a part was complete.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2016
• First Posted: April 13, 2016
• Study Start: September 1, 2016
• Primary Completion: September 25, 2017
• Study Completion: September 25, 2017
• Last Updated: August 12, 2019
• Results First Posted: August 12, 2019

Record last verified: 2019-06