LY3214996 +/- HCQ in Pancreatic Cancer

NCT04386057 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-529
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief Summary

This study is evaluating the safety and efficacy of combining the study drug LY3214996 with hydroxychloroquine sulfate (HCQ) in patients with advanced pancreatic cancer.

Conditions

Pancreatic Cancer; Advanced Cancer

Keywords

Pancreatic Cancer; Advanced Cancer; Extracellular Signal-Regulated Kinases; Cell Growth Inhibitors

Outcome Measures

Primary Outcomes (2)

• Disease Control Rate (DCR)

  Anti-tumor activity will be measured via disease control rate (DCR), which will be defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease (SD) that persists for ≥ 4 months. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  28 Months

• Dose Limiting Toxicity-Lead In

  Dose Limiting Toxicity-Lead In

  28 Days

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  28 Months

• Progression-free Survival (PFS)

  time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation up to 28 Months

• Overall Survival (OS)

  Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. OS was calculated for a median of 115 days, ranging from 18 - 327 days.

Study Arms (4)

Safety Lead-In Cohort

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits. A treatment cycle will be defined as 28 consecutive days. Treatment will be administered on an outpatient basis. Test the safety of study drugs in combination and define dose levels. * LY3214996 * HCQ

Drug: Hydroxychloroquine Sulfate; Drug: LY3214996

LY3214996 and HCQ Combination

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits. A treatment cycle will be defined as 28 consecutive days. Treatment will be administered on an outpatient basis. Combined dosage per determined Lead-In Cohort * LY3214996 * HCQ

Drug: Hydroxychloroquine Sulfate; Drug: LY3214996

LY3214996-Monotherapy

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits. A treatment cycle will be defined as 28 consecutive days.Treatment will be administered on an outpatient basis. -LY3214996

Drug: LY3214996

Cross Over Arm

EXPERIMENTAL

Participants who are enrolled to Arm 2 who experience radiologic disease progression on monotherapy will have the option to cross-over to receive treatment with the combination. Crossover will occur at the treating investigator's discretion following consultation and approval from the overall principal investigator. Combined dosage per determined Lead-In Cohort * LY3214996 * HCQ

Drug: Hydroxychloroquine Sulfate; Drug: LY3214996

Interventions

Hydroxychloroquine Sulfate DRUG

HCQ will be administered by mouth twice daily continuously throughout each treatment per 28 day cycle

Also known as: Plaquenil®), HCQ

Cross Over Arm; LY3214996 and HCQ Combination; Safety Lead-In Cohort

LY3214996 DRUG

LY3214996-daily oral dosage per protocol per 28 day cycle

Cross Over Arm; LY3214996 and HCQ Combination; LY3214996-Monotherapy; Safety Lead-In Cohort

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the pancreas.
• Age ≥ 18 years.
• ECOG performance status ≤ 1
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.
• Participants must have received at least one but no more than two prior lines of systemic therapy for metastatic pancreatic cancer. Perioperative treatment (chemotherapy and/or radiation) is not considered a prior line of therapy.
• Participants must have adequate organ and marrow function as defined below:
• Absolute Neutrophil Count ≥ 1,500/mcL
• Platelet Count ≥ 100,000/mcL
• Total Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
• AST (SGOT) / ALT(SGPT) ≤ 2.5 × institutional ULN, OR
• AST (SGOT) / ALT (SGPT) ≤ 5 × institutional ULN if elevation is a result of metastases
• Creatinine ≤ 1.5 × institutional ULN, OR
• Creatinine Clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above 1.5 × institutional normal (calculated via the Cockcroft-Gault equation)
• The effects of LY3214996 or HCQ on the developing human fetus are unknown. For this reason and because anti-cancer agents are known to be teratogenic, women of child bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of LY3214996 or HCQ administration.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Participants with pancreatic histologies other than adenocarcinoma or poorly differentiated carcinoma, such as neuroendocrine or acinar cell carcinoma.
• Participants who have received a prior MAPK pathway inhibitor, including but not limited to LY3214996.
• Participants who have had systemic chemotherapy, other investigational therapy, or immunotherapy within 3 weeks prior to the first dose of study medication.
• Participants who have received oral tyrosine kinase inhibitors (TKIs) within 5 half-lives of the first dose of study medication.
• Participants who have received radiation therapy within 2 weeks prior to the first dose of study medication.
• Participants who have had major surgery within 4 weeks prior to the first dose of study medication.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to LY3214996 or HCQ. Individuals with a history of a different malignancy are ineligible with the following exceptions: individuals who have been treated and are disease-free for a minimum of 3 years prior to study enrollment, or individuals who are deemed by the treating investigator to be at low risk for disease recurrence. Additionally, individuals with the following cancers are eligible if diagnosed and curatively treated within the past 3 years: basal or squamous cell carcinomas of the skin, and breast or cervical carcinomas in situ.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because LY3214996 and HCQ are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LY3214996 or HCQ, breastfeeding should be discontinued if the mother is treated with LY3214996 or HCQ. A negative serum pregnancy test is required for women of childbearing potential prior to the first dose of study medication.
• Participants who are known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B or C.
• Participants with a history or findings of central or branch retinal artery or venous occlusion with significant vision loss, or other retinal diseases causing visual impairment or would likely cause visual impairment over the time period of the study, as assessed by an ophthalmologist.
• Participants with a known personal or family history of long QT syndrome.
• Participants with known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Participants who are known at the time of trial enrollment to require concomitant treatment with strong CYP3A4 inhibitors or inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference.

Sponsors & Collaborators

• Kimberly Perez, MD: lead
• Eli Lilly and Company: collaborator

Study Sites (4)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Hydroxychloroquine; LY3214996

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Kimberly Perez, MD
• Organization: Dana-Farber Cancer Institute

Kimberly_Perez@DFCI.HARVARD.EDU

617-632-5370

Study Officials

• Kimberly Perez, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: May 10, 2020
• First Posted: May 13, 2020
• Study Start: May 27, 2020
• Primary Completion: August 9, 2023
• Study Completion: February 5, 2024
• Last Updated: February 12, 2025
• Results First Posted: November 27, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)