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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03092934
• Collaborator: AurKa Pharma Inc. (Other)
• Enrollment: 13
• Locations: 3
• Arms: 4
• Actual Duration (Months): 34.7
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms; Neoplasm Metastasis; Triple Negative Breast Neoplasms; Head and Neck Neoplasms; Breast Neoplasms; Solid Tumor, Adult; Small Cell Lung Carcinoma	Drug: LY3295668	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Open-Label
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 29, 2017
• Actual Primary Completion Date: Apr 20, 2020
• Actual Study Completion Date: Apr 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 25 milligrams (mg) LY3295668 (Phase 1) 25 milligrams (mg) LY3295668 twice daily (BID) administered orally in 21-day cycles.	Drug: LY3295668; Oral capsules; Other Names: AK-01 Erbumine
Experimental: 50 mg LY3295668 (Phase 1) 50 mg LY3295668 BID administered orally in 21-day cycles.	Drug: LY3295668; Oral capsules; Other Names: AK-01 Erbumine
Experimental: 75 mg LY3295668 (Phase 1) 75 mg LY3295668 BID administered orally in 21-day cycles.	Drug: LY3295668; Oral capsules; Other Names: AK-01 Erbumine
Experimental: 25 mg LY3295668 (Phase 2) 25 mg LY3295668 BID administered orally in 21-day cycles.	Drug: LY3295668; Oral capsules; Other Names: AK-01 Erbumine

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
2	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
3	McGill University	Montreal	Quebec	Canada	H4A 3J1

Sponsors and Collaborators

• Eli Lilly and Company
• AurKa Pharma Inc.

Investigators

• Study Director: 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 Documents (Full-Text)

• Study Protocol - Apr 10, 2018
• Statistical Analysis Plan - Feb 6, 2019

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03092934
• Other Study ID Numbers: 17228; AURA-001; J1O-MC-JZHA
• First Posted: Mar 28, 2017
• Last Update Posted: Jul 2, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Neoplasm Metastasis; Breast Neoplasms; Head and Neck Neoplasms; Small Cell Lung Carcinoma; Triple Negative Breast Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	Phase I participants are said to have completed the study if they completed Dose Limiting Toxicity (DLT) period or have had a DLT. Phase II participants who died or are alive and on study at conclusion but off treatment are defined as completed.

Arm/Group Title	25 Milligrams (mg) LY3295668 (Phase 1)	50 mg LY3295668 (Phase 1)	75 mg LY3295668 (Phase 1)	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 twice daily (BID) administered orally in 21-day cycles.	50 mg LY3295668 BID administered orally in 21-day cycles.	75 mg LY3295668 BID administered orally in 21-day cycles.	25 mg LY3295668 BID administered orally in 21-day cycles.
Period Title: Overall Study
STARTED	8	2	2	1
Received at Least One Dose of Study Drug	8	2	2	1
COMPLETED	8	2	2	1
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	25 Milligrams (mg) LY3295668 (Phase 1)	50 mg LY3295668 (Phase 1)	75 mg LY3295668 (Phase 1)	25 mg LY3295668 (Phase 2)	Total
Arm/Group Description	25 mg LY3295668 twice daily (BID) administered orally in 21-day cycles.	50 milligrams (mg) LY3295668 BID administered orally in 21-day cycles. LY3295668: Oral capsules	75 mg LY3295668 BID administered orally in 21-day cycles. LY3295668: Oral capsules	25 mg LY3295668 BID administered orally in 21-day cycles. LY3295668: Oral capsules	Total of all reporting groups
Overall Participants	8	2	2	1	13
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 87.5%	0 0%	0 0%	0 0%	7 53.8%
>=65 years	1 12.5%	2 100%	2 100%	1 100%	6 46.2%
Sex: Female, Male (Count of Participants)
Female	4 50%	1 50%	2 100%	1 100%	8 61.5%
Male	4 50%	1 50%	0 0%	0 0%	5 38.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	2 100%	2 100%	1 100%	13 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 12.5%	0 0%	0 0%	0 0%	1 7.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	5 62.5%	2 100%	2 100%	1 100%	10 76.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 25%	0 0%	0 0%	0 0%	2 15.4%
Region of Enrollment (Count of Participants)
Canada	8 100%	2 100%	2 100%	1 100%	13 100%

Outcome Measures

1. Primary Outcome

Title	Phase 1: Maximum Tolerated Dose
Description	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.
Time Frame	Cycle 1 (21 days)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and experienced a DLT; or received ≥ 38 doses of study drug in Cycle 1 and were not discontinued from the study before completing Cycle 1.

Arm/Group Title	LY3295668 Phase 1
Arm/Group Description	25 milligrams (mg) LY3295668 twice daily (BID) administered orally in 21-day cycles.
Measure Participants	12
Number [milligram (mg)]	25

2. Primary Outcome

Title	Phase 2: Percentage of Participants Who Achieved Partial Response (PR) or Complete Response (CR) [Objective Response Rate (ORR)]
Description	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.
Time Frame	Baseline to Objective Disease Progression (Up to 11 months)

Outcome Measure Data

Analysis Population Description

All patients who received at least 1 dose of AK-01, whether or not they completed all protocol requirements.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	1
Number [percentage of participants]	0 0%

3. Secondary Outcome

Title	Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events
Description	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.
Time Frame	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug, whether or not they completed all protocol requirements.

Arm/Group Title	25 mg LY3295668 (Phase 1)	50 mg LY3295668 (Phase 1)	75 mg LY3295668 (Phase 1)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.	50 mg LY3295668 BID administered orally in 21-day cycles.	75 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	8	2	2
Count of Participants [Participants]	7 87.5%	2 100%	2 100%

4. Secondary Outcome

Title	Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events
Description	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.
Time Frame	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug whether or not they completed all protocol requirements.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	1
Count of Participants [Participants]	1 12.5%

5. Secondary Outcome

Title	Phase 2: Pharmacokinetic (PK): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC[0-12]) (Phase 2)
Description	Area under the plasma concentration-time curve for LY3295668 from time zero to 12 hours.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Zero participants analyzed due to data not collected.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	0

6. Secondary Outcome

Title	Phase 2: PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC[0-24])
Description	Area under the plasma concentration-time curve for LY3295668 from time zero to 24 hours.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Zero participants analyzed due to data not collected.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	0

7. Secondary Outcome

Title	Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)
Description	Maximum observed plasma concentration for LY3295668.
Time Frame	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data in Phase 2 per protocol.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	1
Day 1	NA (NA)
Day 15	NA (NA)

8. Secondary Outcome

Title	Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)
Description	Time of maximum observed plasma concentration of LY3295668.
Time Frame	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data in Phase 2 per protocol.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	1
Day 1	NA (NA)
Day 15	NA (NA)

9. Secondary Outcome

Title	Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)
Description	Apparent terminal elimination half-life of LY3295668.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Zero participants analyzed due to data not collected.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	0

10. Secondary Outcome

Title	Phase 2: PK: Apparent Total Plasma Clearance (CL/F)
Description	Apparent total plasma clearance of LY3295668.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Zero participants analyzed due to data not collected.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	0

11. Secondary Outcome

Title	Phase 2: PK: Apparent Volume of Distribution (Vz/F)
Description	Apparent volume of distribution of LY3295668.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Zero participants analyzed due to data not collected.

Arm/Group Title	25 mg LY3295668 (Phase 2)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	0

12. Secondary Outcome

Title	Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 White Blood Cell Count (WBC)
Description	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.
Time Frame	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug, whether or not they completed all protocol requirements in Phase 1 per protocol.

Arm/Group Title	25 mg LY3295668 (Phase 1)	50 mg LY3295668 (Phase 1)	75 mg LY3295668 (Phase 1)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.	50 mg LY3295668 BID administered orally in 21-day cycles.	75 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	8	2	2
Count of Participants [Participants]	1 12.5%	0 0%	0 0%

13. Secondary Outcome

Title	Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Neutrophils (Segmented and Blended)
Description	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.
Time Frame	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug, whether or not they completed all protocol requirements in Phase 1 per protocol.

Arm/Group Title	25 mg LY3295668 (Phase 1)	50 mg LY3295668 (Phase 1)	75 mg LY3295668 (Phase 1)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.	50 mg LY3295668 BID administered orally in 21-day cycles.	75 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	8	2	2
Count of Participants [Participants]	1 12.5%	0 0%	1 50%

14. Secondary Outcome

Title	Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Lymphocytes
Description	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.
Time Frame	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug, whether or not they completed all protocol requirements in Phase 1 per protocol.

Arm/Group Title	25 mg LY3295668 (Phase 1)	50 mg LY3295668 (Phase 1)	75 mg LY3295668 (Phase 1)
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles.	50 mg LY3295668 BID administered orally in 21-day cycles.	75 mg LY3295668 BID administered orally in 21-day cycles.
Measure Participants	8	2	2
Count of Participants [Participants]	2 25%	1 50%	0 0%

Adverse Events

Time Frame	Up to 29 Months
Adverse Event Reporting Description	All participants who received at least one dose of study drug, whether or not they completed all protocol requirements. Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
Arm/Group Title	25 Milligrams (mg) LY3295668		50 mg LY3295688		75 mg LY3295688
Arm/Group Description	25 mg LY3295668 BID administered orally in 21-day cycles. Phase 1 and Phase 2 participants have been combined.		50 mg LY3295668 BID administered orally in 21-day cycles.		75 mg LY3295668 BID administered orally in 21-day cycles
All Cause Mortality
	25 Milligrams (mg) LY3295668		50 mg LY3295688		75 mg LY3295688
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		0/2 (0%)		0/2 (0%)
Serious Adverse Events
	25 Milligrams (mg) LY3295668		50 mg LY3295688		75 mg LY3295688
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)		1/2 (50%)		2/2 (100%)
Cardiac disorders
Pericardial effusion	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Eye disorders
Corneal deposits	0/9 (0%)	0	0/2 (0%)	0	1/2 (50%)	1
Gastrointestinal disorders
Diarrhoea	0/9 (0%)	0	1/2 (50%)	1	1/2 (50%)	1
Stomatitis	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
General disorders
Mucosal inflammation	0/9 (0%)	0	0/2 (0%)	0	1/2 (50%)	1
Infections and infestations
Influenza	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Pneumocystis jirovecii pneumonia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Pneumonia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Nervous system disorders
Presyncope	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleuritic pain	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	25 Milligrams (mg) LY3295668		50 mg LY3295688		75 mg LY3295688
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/9 (100%)		2/2 (100%)		2/2 (100%)
Blood and lymphatic system disorders
Anaemia	2/9 (22.2%)	34	1/2 (50%)	1	0/2 (0%)	0
Febrile neutropenia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Neutropenia	0/9 (0%)	0	0/2 (0%)	0	1/2 (50%)	1
Cardiac disorders
Palpitations	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Ear and labyrinth disorders
Ear discomfort	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Vertigo	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Eye disorders
Eye pruritus	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Lacrimation increased	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Night blindness	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Vision blurred	1/9 (11.1%)	1	0/2 (0%)	0	1/2 (50%)	1
Gastrointestinal disorders
Abdominal pain	2/9 (22.2%)	2	1/2 (50%)	1	0/2 (0%)	0
Abdominal pain upper	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Anal fistula	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Ascites	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Constipation	2/9 (22.2%)	4	1/2 (50%)	1	1/2 (50%)	1
Diarrhoea	4/9 (44.4%)	6	1/2 (50%)	1	2/2 (100%)	2
Dyspepsia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Flatulence	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Gastrointestinal haemorrhage	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Gastrooesophageal reflux disease	2/9 (22.2%)	3	0/2 (0%)	0	0/2 (0%)	0
Gingival recession	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Glossodynia	1/9 (11.1%)	2	0/2 (0%)	0	0/2 (0%)	0
Haemorrhoids	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Large intestinal haemorrhage	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Mouth ulceration	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Nausea	2/9 (22.2%)	2	0/2 (0%)	0	2/2 (100%)	2
Rectal haemorrhage	2/9 (22.2%)	3	0/2 (0%)	0	0/2 (0%)	0
Stomatitis	4/9 (44.4%)	5	0/2 (0%)	0	0/2 (0%)	0
Vomiting	2/9 (22.2%)	4	0/2 (0%)	0	0/2 (0%)	0
General disorders
Asthenia	2/9 (22.2%)	2	1/2 (50%)	1	0/2 (0%)	0
Chest pain	2/9 (22.2%)	2	0/2 (0%)	0	0/2 (0%)	0
Fatigue	5/9 (55.6%)	6	0/2 (0%)	0	0/2 (0%)	0
Mucosal inflammation	1/9 (11.1%)	1	2/2 (100%)	4	2/2 (100%)	3
Pain	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Peripheral swelling	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Pyrexia	3/9 (33.3%)	3	1/2 (50%)	1	0/2 (0%)	0
Immune system disorders
Hypersensitivity	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Infections and infestations
Cellulitis	0/9 (0%)	0	0/2 (0%)	0	1/2 (50%)	1
Gingivitis	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Infection	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Nasopharyngitis	2/9 (22.2%)	2	0/2 (0%)	0	0/2 (0%)	0
Pneumonia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Injury, poisoning and procedural complications
Skin abrasion	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Investigations
Alanine aminotransferase increased	1/9 (11.1%)	4	0/2 (0%)	0	0/2 (0%)	0
Aspartate aminotransferase increased	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Blood alkaline phosphatase increased	2/9 (22.2%)	2	1/2 (50%)	1	0/2 (0%)	0
Blood creatinine increased	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Blood lactate dehydrogenase increased	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Gamma-glutamyltransferase increased	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Platelet count decreased	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Weight decreased	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	2/9 (22.2%)	4	1/2 (50%)	1	1/2 (50%)	1
Failure to thrive	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Hypokalaemia	1/9 (11.1%)	2	0/2 (0%)	0	0/2 (0%)	0
Hypophosphataemia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Arthritis	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Back pain	2/9 (22.2%)	4	0/2 (0%)	0	0/2 (0%)	0
Musculoskeletal pain	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Pain in extremity	1/9 (11.1%)	2	0/2 (0%)	0	0/2 (0%)	0
Pain in jaw	0/9 (0%)	0	0/2 (0%)	0	1/2 (50%)	1
Nervous system disorders
Dizziness	0/9 (0%)	0	1/2 (50%)	1	1/2 (50%)	1
Headache	2/9 (22.2%)	2	0/2 (0%)	0	0/2 (0%)	0
Hyperaesthesia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Paraesthesia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Parosmia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Psychiatric disorders
Depression	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Renal and urinary disorders
Urinary hesitation	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Reproductive system and breast disorders
Menstruation irregular	1/5 (20%)	1	0/1 (0%)	0	0/2 (0%)	0
Vulvovaginal pain	0/5 (0%)	0	0/1 (0%)	0	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/9 (22.2%)	3	0/2 (0%)	0	0/2 (0%)	0
Dysphonia	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Dyspnoea	4/9 (44.4%)	4	0/2 (0%)	0	0/2 (0%)	0
Nasal discomfort	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Oropharyngeal pain	0/9 (0%)	0	0/2 (0%)	0	1/2 (50%)	1
Painful respiration	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Productive cough	1/9 (11.1%)	2	0/2 (0%)	0	0/2 (0%)	0
Rhinorrhoea	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Sinus congestion	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Throat irritation	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	2/9 (22.2%)	2	1/2 (50%)	1	2/2 (100%)	2
Dry skin	1/9 (11.1%)	1	0/2 (0%)	0	0/2 (0%)	0
Erythema	0/9 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Hyperhidrosis	1/9 (11.1%)	1	0/2 (0%)	0	1/2 (50%)	1
Onychoclasis	2/9 (22.2%)	2	0/2 (0%)	0	0/2 (0%)	0
Palmar-plantar erythrodysaesthesia syndrome	0/9 (0%)	0	1/2 (50%)	2	0/2 (0%)	0
Rash	1/9 (11.1%)	1	1/2 (50%)	5	0/2 (0%)	0

Limitations/Caveats

Study terminated due to sponsor decision.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.