A Study of AK-01 (LY3295668) in Solid Tumors

Neoplasms Clinical Trial

Official title:

A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of AK-01 as Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03092934
• Other study ID #: 17228
• Secondary ID: AURA-001J1O-MC-J
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 29, 2017
• Est. completion date: April 20, 2020

Study information

• Verified date: June 2021
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This two-part study consists of a phase 1 dose escalation study in participants with locally advanced or metastatic solid tumors, and a phase 2 portion in up to 3 groups with either small cell lung cancer, breast cancer and/or one other solid tumor type.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: April 20, 2020
• Est. primary completion date: April 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have received at least 1 but no more than 4 prior systemic therapies

• Have adequate organ function

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have estimated life expectancy greater than or equal to (=)12 weeks

• Have fully recovered from radiation therapy or surgery, and are recovering from any acute adverse effects of other cancer therapies

• Have discontinued all chemotherapy, investigational therapy, molecularly-targeted therapy, and cancer-related hormonal therapy at least 14 days prior, biologic or immunotherapeutic therapy at least 21 days prior, or mitomycin-C or nitrosoureas at least 6 weeks prior

• Female participants with reproductive potential agree to use 2 forms of highly effective contraception during the study and for the following 3 months

• Male participants must use a barrier method of contraception during the study and for the following 3 months

Phase 1

• Have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor)

Phase 2

• Have disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1

• Have evidence of a solid tumor that is locally advanced and/or metastatic, and in:

• Small Cell Lung Cancer (SCLC), must have failed platinum-containing therapy

• Breast Cancer, be Estrogen Receptor positive and/or Progesterone Receptor positive, but Human Epidermal Growth Factor Receptor 2 (HER2) negative, and must have failed a hormone therapy and a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor

• Triple negative breast cancer (TNBC) and failed standard therapy

• Squamous cell cancers of the head neck associated with the human papilloma virus (HPV), and have failed standard therapy

• Other solid tumor type that has been approved by the sponsor

Exclusion Criteria:

• Have symptomatic central nervous system (CNS) metastasis (unless asymptomatic and not current receiving corticosteroids) or a primary tumor of the CNS

• Have a medical condition that precludes participation (swallowing disorder, organ transplant, pregnant or nursing, HIV, active Hepatitis B or C, cardiac disease, history of major surgery in upper gastrointestinal (GI) tract or GI disease, hypokalemia, hypomagnesaemia or hypocalcaemia that cannot be controlled)

Related Conditions & MeSH terms

• Breast Neoplasms
• Head and Neck Neoplasms
• Neoplasm Metastasis
• Neoplasms
• Small Cell Lung Carcinoma
• Solid Tumor, Adult
• Triple Negative Breast Neoplasms

Intervention

Drug:
• LY3295668
Oral capsules

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	AurKa Pharma Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Maximum Tolerated Dose	Maximum Tolerated Dose (MTD) was defined as the dose immediately below the dose at which =2/3, =2/6, or =3/9 participants in a cohort experienced a dose limiting toxicity (DLT) during the first 21 days of treatment (Cycle 1) in Phase 1.	Cycle 1 (21 days)
Primary	Phase 2: Percentage of Participants Who Achieved Partial Response (PR) or Complete Response (CR) [Objective Response Rate (ORR)]	Objective response rate (ORR) was defined as a percentage of responders who achieved complete response or partial response (CR+PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Complete response (CR) is defined as disappearance of all target (and non-target) lesions, and no appearance of new lesion. Partial response (PR) was defined as at least a 30% decrease in the sum of longest diameters (LD) of target lesions, taking as reference the baseline sum of LD, no progression of non-target lesions, and no appearance of new lesions.	Baseline to Objective Disease Progression (Up to 11 months)
Secondary	Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events	A treatment-emergent adverse event (AE) is an AE that started or worsened (increased in severity) from the treatment start date to 30 days after the treatment end date. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Secondary	Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events	A treatment-emergent adverse event (AE) is an AE that started or worsened (increased in severity) from the treatment start date to 30 days after the treatment end date. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Secondary	Phase 2: Pharmacokinetic (PK): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC[0-12]) (Phase 2)	Area under the plasma concentration-time curve for LY3295668 from time zero to 12 hours.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 - 12 hours postdose; Cycle 1: Day 2 and Day 8 predose
Secondary	Phase 2: PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC[0-24])	Area under the plasma concentration-time curve for LY3295668 from time zero to 24 hours.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8-12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose
Secondary	Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration for LY3295668.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose
Secondary	Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)	Time of maximum observed plasma concentration of LY3295668.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose
Secondary	Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)	Apparent terminal elimination half-life of LY3295668.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8-12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose
Secondary	Phase 2: PK: Apparent Total Plasma Clearance (CL/F)	Apparent total plasma clearance of LY3295668.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 -12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose
Secondary	Phase 2: PK: Apparent Volume of Distribution (Vz/F)	Apparent volume of distribution of LY3295668.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 -12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose
Secondary	Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 White Blood Cell Count (WBC)	Presented are participants with the worst post-baseline WBC Grade >= 3 using the National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events version 4.03 (CTCAE v4.03). where Grade 1: < Lower Limit Normal (LLN) - 3000/mm3;	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Secondary	Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Neutrophils (Segmented and Blended)	Presented are participants with the worst post-baseline neutrophils Grade >=3 using the NCI-CTCAE v4.03 where Grade 1: < LLN - 1500/mm3;	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Secondary	Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Lymphocytes	Presented are participants with the worst post-baseline lymphocytes Grade >=3 using the NCI-CTCAE version 4.03 where Grade 1:	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)