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

Phase 1

Completed

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

Interventions: Drug: LY3295668

Registration Number: NCT03092934

Lead Sponsor: Eli Lilly and Company

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
75 mg LY3295668 (Phase 1)	LY3295668	75 mg LY3295668 BID administered orally in 21-day cycles.
25 mg LY3295668 (Phase 2)	LY3295668	25 mg LY3295668 BID administered orally in 21-day cycles.
25 milligrams (mg) LY3295668 (Phase 1)	LY3295668	25 milligrams (mg) LY3295668 twice daily (BID) administered orally in 21-day cycles.
50 mg LY3295668 (Phase 1)	LY3295668	50 mg LY3295668 BID administered orally in 21-day cycles.

Primary Outcome Measures

Name	Time	Method
Phase 1: Maximum Tolerated Dose	Cycle 1 (21 days)	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.
Phase 2: Percentage of Participants Who Achieved Partial Response (PR) or Complete Response (CR) [Objective Response Rate (ORR)]	Baseline to Objective Disease Progression (Up to 11 months)	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.

Secondary Outcome Measures

Name	Time	Method
Phase 2: Pharmacokinetic (PK): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC[0-12]) (Phase 2)	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	Area under the plasma concentration-time curve for LY3295668 from time zero to 12 hours.
Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)	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	Apparent terminal elimination half-life of LY3295668.
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Neutrophils (Segmented and Blended)	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)	Presented are participants with the worst post-baseline neutrophils Grade \>=3 using the NCI-CTCAE v4.03 where Grade 1: \< LLN - 1500/mm3; \<LLN - 1.5 x10e9/L, Grade 2: \<1500 - 1000/mm3; \<1.5 - 1.0 x10e9/L, Grade 3: \<1000 - 500/mm3; \<1.0 - 0.5 x10e9/L, Grade 4: \<500/mm3; \<0.5 x 10e9/L.
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Lymphocytes	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)	Presented are participants with the worst post-baseline lymphocytes Grade \>=3 using the NCI-CTCAE version 4.03 where Grade 1: \<LLN - \<800/mm3, \<LLN - 0.8 x 10e9/L, Grade 2: \<800 - 500/mm3; \<0.8 - 0.5 x 10e9/L, Grade 3: \<500 - 200/mm3; \<0.5 - 0.2 x 10e9/L, \<200mm3; \<0.2 x 10e9/L.
Phase 2: PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC[0-24])	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	Area under the plasma concentration-time curve for LY3295668 from time zero to 24 hours.
Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)	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.
Phase 2: PK: Apparent Total Plasma Clearance (CL/F)	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	Apparent total plasma clearance of LY3295668.
Phase 2: PK: Apparent Volume of Distribution (Vz/F)	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	Apparent volume of distribution of LY3295668.
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 White Blood Cell Count (WBC)	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)	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; \<LLN - 3.0 x10e9/L, Grade 2: \<3000 - 2000/mm3; \<3.0 - 2.0 x10e9/L, Grade 3: \<2000 - 1000/mm3; \<2.0 1.0 x10e9/L, Grade 4: \<1000/mm3; \<1.0 x10e9/L.
Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)	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.
Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose	Maximum observed plasma concentration for LY3295668.
Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose	Time of maximum observed plasma concentration of LY3295668.

Trial Locations

Locations (3): Cross Cancer Institute
🇨🇦
Edmonton, Alberta, Canada
McGill University
🇨🇦
Montreal, Quebec, Canada
Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada