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All Drugs and Chemicals

Antibodies

Immunoglobulins

LY3381916 administered orally and LY3300054 administered intravenously (IV).

Metastatic triple negative breast cancer (TNBC)

LY3381916 administered orally and LY3300054 administered IV.

Metastatic non-small cell lung cancer (NSCLC)

LY3381916 administered orally and LY3300054 administered IV.

Metastatic clear cell carcinoma renal cell carcinoma (RCC)

LY3381916 administered orally and LY3300054 administered IV.

LY3381916

LY3300054

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)

The purpose of this study is to evaluate the safety of the study drug LY3381916 administered alone or in combination with anti-programmed cell death ligand 1 (PD-L1) checkpoint antibody (LY3300054).

A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors

A Phase 1a/1b Study of an Anti-IDO-1 Agent (LY3381916) Administered Alone or in Combination With Anti- PD-L1 Checkpoint Antibody (LY3300054) in Solid Tumors

PK: Cmax of LY3381916 administered in combination with LY3300054

PK: AUC of LY3381916 administered in combination with LY3300054

PK: Cmax of LY3300054 administered in combination with LY3381916

PK: Cmin of LY3300054 administered in combination with LY3381916

ORR: Percentage of participants with a CR or PR

DCR: Percentage of participants who exhibit SD, CR or PR

Eli Lilly and Company

Carcinoma, Squamous Cell

Melanoma

Squamous Cell Carcinoma of Head and Neck

Vasoconstrictor Agents

Antineoplastic Agents

Norepinephrine

Nivolumab

Ipilimumab

Serotonin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.

Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.

Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.

Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.

Participants with unresectable or metastatic melanoma (MEL) were planned to be included in this cohort, who did not receive prior systemic therapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.

Participants with advanced or metastatic non-small cell lung cancer (NSCLC) were planned to be included in this cohort, who have received no more than 1 prior line of platinum-based chemotherapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.

Participants with recurrent or metastatic serotonin norepinephrine reuptake inhibitor (SCCHN) were planned to be included in this cohort, who received no more than 1 prior line of platinum-based chemotherapy for recurrent or metastatic disease to receive epacadostat in combination with nivolumab and lirilumab at the MTD/PAD determined from dose escalation phase.

Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.

Epacadostat

Nivolumab at the protocol-specified dose and schedule.

Ipilimumab at the protocol-specified dose and schedule.

Lirilumab at the protocol-specified dose and schedule.

Lirilumab

Medical Monitor Consultant for Incyte

The purpose of this study is to determine the safety, tolerability, and efficacy of epacadostat when given in combination with nivolumab and ipilimumab, and in combination with nivolumab and lirilumab, in participant with advanced or metastatic malignancies.

A Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Participants With Advanced or Metastatic Malignancies (ECHO-208)

A Phase 1/2, Open-Label, Dose-Escalation, Safety, Tolerability, and Efficacy Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies (ECHO-208)

A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.

ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

DOR was defined as the time from the earliest date of CR or PR until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.

PFS was defined as the time from the start of combination therapy until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.

A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.

Incyte Corporation

Safety population included all participants enrolled in the study who received at least 1 dose of combination therapy.

Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID

Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Weight

Height

Full analysis set included all participants enrolled in the study who received at least 1 dose of combination therapy.

Study Director

Safety population included all participants enrolled in the study who received at least 1 dose of combination therapy. Treatment group B was excluded from this analysis as no participants were enrolled.

Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs)

Phase 2: Dose Expansion: Treatment Group A: Cohort A1

Phase 2: Dose Expansion: Treatment Group A: Cohort A2

Phase 2: Dose Expansion: Treatment Group B: Cohort B1

As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.

Phase 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID

Phase 1: Objective Response Rate (ORR) Based on RECIST v1.1

Phase 1: Duration of Response (DOR)

Phase 1: Progression-free Survival (PFS)

Phase 2: Duration of Response (DOR)

Phase 2: Progression-free Survival (PFS)

Phase 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

Phase 1: Dose Escalataion: Treatment Group A: Cohort 1 Epacadostat 50 mg BID

Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID

Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID

Overall Study

Symptoms and General Pathology

Recurrence

Disease Progression

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Psychotropic Drugs

Amino Acids

Vaccines

Docetaxel

Immunomodulating Agents

Tryptophan

Tubulin Modulators

Antimitotic Agents

Antidepressive Agents

Up to 18 participants will be enrolled and treated at escalating doses of Indoximod with a fixed dose of tergenpumatucel-L and docetaxel. Treatment may continue until definitive disease progression or significant toxicology.

Tergenpumatucel-L

Indoximod

Gene Kennedy, MD

This is a Phase 1/2 trial using indoximod, an inhibitor of the immune "checkpoint" pathway indoleamine 2,3-dioxygenase (IDO), in combination with Tergenpumatucel-L immunotherapy and Docetaxel to treat subjects with advanced Non-Small Cell Lung Cancer (NSCLC). From a practical standpoint, a successful tumor immunotherapy will likely require a combination treatment with additional therapeutic interventions that both activate an immune response and remove redundant mechanisms of tolerance maintenance. This clinical trial utilizes the combination of the chemotherapeutic agent, docetaxel, plus two investigational methods of cancer immunotherapy: the first, tergenpumatucel-L, is intended to educate the human immune system to recognize the abnormal components found in lung cancer cells, resulting in an immune response intended to destroy or block the growth of the cancer; and the second, the IDO inhibitor Indoximod, will overcome tumor-induced immune suppression.

The goal of this study is to assess the progression-free survival (PFS) and overall survival (OS) rates in this patient population. This study will provide a foundation for future trials testing indoximod combined with tergenpumatucel-L.

Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer

A Phase 1b/2 Study of Tergenpumatucel-L (HyperAcute Lung) Immunotherapy in Combination With the IDO Pathway Inhibitor Indoximod and Docetaxel in Patients With Advanced Previously Treated Non-Small Cell Lung Cancer (NSCLS)

Phase 1 component: To identify the regimen limiting toxicity (RLT) for the combination of tergenpumatucel-L and indoximod.

To assess preliminary evidence of efficacy of tergenpumatuucel-L, indoximod and docetaxel using RECIST 1.1 measurement criteria.

Assess evidence of delayed response of tergenpumatuucel-L, indoximod and docetaxel using RECIST 1.1 measurement criteria.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors	NCT03343613	Solid Tumor Non Small Cell ... Renal Cell Carc... Triple Negative...	LY3381916 LY3300054	18 Years -	Eli Lilly and Company
A Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Participants With Advanced or Metastatic Malignancies (ECHO-208)	NCT03347123	Solid Tumors	Epacadostat Nivolumab Ipilimumab Lirilumab	18 Years -	Incyte Corporation
A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors	NCT03343613	Solid Tumor Non Small Cell ... Renal Cell Carc... Triple Negative...	LY3381916 LY3300054	18 Years -	Eli Lilly and Company
Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer	NCT02460367	Non-small Cell ... Progression of ... Non-small Cell ...	Docetaxel Tergenpumatucel... Indoximod	18 Years -	Lumos Pharma
Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer	NCT02460367	Non-small Cell ... Progression of ... Non-small Cell ...	Docetaxel Tergenpumatucel... Indoximod	18 Years -	Lumos Pharma
Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer	NCT02460367	Non-small Cell ... Progression of ... Non-small Cell ...	Docetaxel Tergenpumatucel... Indoximod	18 Years -	Lumos Pharma

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