A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549

NCT02637531 | Unknown Phase 1

• 1 other identifier: IPI-549-01
• Study Type: interventional
• Target: 219
• Locations: 1 country
• Sites: 11

Brief Summary

This dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IPI-549 monotherapy and IPI-549 in combination with nivolumab in subjects with advanced solid tumors.

Conditions

Advanced Solid Tumors (Part A/B/C/D); Non-small Cell Lung Cancer (Part E); Melanoma (Part E); Squamous Cell Cancer of the Head and Neck (Part E); Triple Negative Breast Cancer (Part F); Adrenocortical Carcinoma (Part G); Mesothelioma (Part G); High-circulating Myeloid-derived Suppressor Cells (Part H)

Keywords

IPI-549; Phase 1; Advanced Solid Tumor; Non-small cell lung cancer; Melanoma; PI3K; Squamous Cell Cancer of the Head and Neck; Triple Negative Breast Cancer; Adrenocortical Carcinoma; Mesothelioma; High-circulating myeloid-derived suppressor cells (MDSCs); eganelisib

Outcome Measures

Primary Outcomes (2)

• Part A/B/C: Dose Limiting Toxicities (DLT)

  From date of initial dose until up to 28 days for IPI-549

• Part D/E: Adverse Events (AE) and safety laboratory values

  Number of patients with Clinically significant abnormal laboratory values and adverse events that are related to treatment from date of initial dose until 30 days after last dose of IPI-549 and 100 days after the last dose of Nivolumab

Secondary Outcomes (28)

• Part A/B: Adverse Events (AE) and safety laboratory values

  Number of patients with Clinically significant abnormal laboratory values and adverse events that are related to treatment assessed during every visit for duration of study participation which is estimated to be 24 months

• Part A/B: Plasma concentrations of IPI-549 (metabolites, as appropriate)

  Assessed during Days 1- 22 of Cycles 1 and 2, Assessed During Day 1 of Cycles 3 and 4

• Part A/B: Overall response rate (ORR), complete response/remission (CR) or partial response/remission (PR)

  Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year

• Part A/B: Duration of response (DoR)

  Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year

• Part C: Adverse Events (AE) and safety laboratory values

  Number of patients with Clinically significant abnormal laboratory values and adverse events that are related to treatment assessed during every visit for duration of study participation which is estimated to be 24 months

Study Arms (11)

Part A/B: IPI-549 Dose Escalation

EXPERIMENTAL

Participants receive IPI-549 orally (PO) once a day (QD) for Part A and twice a day (BID) in Part B until disease progression.

Drug: IPI-549 (eganelisib)

Part C: IPI-549 and nivolumab

EXPERIMENTAL

Participants receive IPI-549 (dose determined from Part A/B) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Part D: IPI-549 Monotherapy

EXPERIMENTAL

Participants receive IPI-549 (dose determined from Part A/B) orally until disease progression.

Drug: IPI-549 (eganelisib)

Part D Annex: IPI-549 and nivolumab

EXPERIMENTAL

Participants receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Part E: NSCLC: IPI-549 and nivolumab

EXPERIMENTAL

Participants with NSCLC receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Part E: Melanoma: IPI-549 and nivolumab

EXPERIMENTAL

Participants with melanoma receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Part E: SCCHN: IPI-549 and nivolumab

EXPERIMENTAL

Participants with squamous cell cancer of the head and neck receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Part F: TNBC: IPI-549 and nivolumab

EXPERIMENTAL

Participants with triple negative breast cancer receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Part G: ACC: IPI-549 and nivolumab

EXPERIMENTAL

Participants with adrenocortical carcinoma receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Part G: Mesothelioma: IPI-549 and nivolumab

EXPERIMENTAL

Participants with mesothelioma receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Part H: High-circulating MDSCs: IPI-549 and nivolumab

EXPERIMENTAL

Participants with high-circulating MDSCs receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks.

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Interventions

IPI-549 (eganelisib) DRUG

IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E)

Part A/B: IPI-549 Dose Escalation; Part C: IPI-549 and nivolumab; Part D Annex: IPI-549 and nivolumab; Part D: IPI-549 Monotherapy; Part E: Melanoma: IPI-549 and nivolumab; Part E: NSCLC: IPI-549 and nivolumab; Part E: SCCHN: IPI-549 and nivolumab; Part F: TNBC: IPI-549 and nivolumab; Part G: ACC: IPI-549 and nivolumab; Part G: Mesothelioma: IPI-549 and nivolumab; Part H: High-circulating MDSCs: IPI-549 and nivolumab

Nivolumab DRUG

Nivolumab (240 mg, Q2W) administered intravenously (IV) in 28-day cycles (Part C/D-Annex/E).

Also known as: OPDIVO

Part C: IPI-549 and nivolumab; Part D Annex: IPI-549 and nivolumab; Part E: Melanoma: IPI-549 and nivolumab; Part E: NSCLC: IPI-549 and nivolumab; Part E: SCCHN: IPI-549 and nivolumab; Part F: TNBC: IPI-549 and nivolumab; Part G: ACC: IPI-549 and nivolumab; Part G: Mesothelioma: IPI-549 and nivolumab; Part H: High-circulating MDSCs: IPI-549 and nivolumab

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age
• Life expectancy of ≥ 3 months
• Histological or cytological evidence of advanced and/or metastatic carcinoma or melanoma , excluding sarcoma
• At least 1 measurable disease lesion as defined by RECIST 1.1
• Serum creatinine clearance ≥ 60 mL/min and serum creatinine ≤ 2.0 x the upper limit of normal (ULN) as determined by either of the following: Estimation as calculated by Cockcroft-Gault equation or Direct measurement by 24-hour urine collection
• Total bilirubin ≤ 1.5 x ULN (unless elevated due to Gilbert's syndrome)
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 x ULN (\<5x ULN if liver metastasis)
• Adequate hematological function, defined as absolute neutrophil count ≥1.5 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (corresponds to Karnofsky Performance Status (KPS) ≥ 60%)
• Subjects entering Part A, B, C, or D must also meet the following additional criterion:
• Failure to respond to standard therapy, or for whom no appropriate therapies are available (based on the judgement of the Investigator)
• Subjects entering Part D, E, F or G must also meet the following additional criterion:
• Willing to undergo 1 pre-treatment and 1 on-treatment tumor biopsy
• Subjects entering Part E must also meet the following additional criteria:
• Histological or cytological evidence of NSCLC, melanoma, , human papillomavirus (HPV) positive or HPV negative SCCHN (oral cavity, pharynx, hypopharynx, larynx, nasopharyngeal \[including undifferentiated nasopharyngeal carcinoma\]), or another tumor type to be determined

You may not qualify if:

• Subjects are to be excluded from the study if they meet any of the following criteria:
• Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any excipient in the study drugs
• Major surgery within 4 weeks prior to Screening
• Subjects who have been treated with chemotherapy, biologic therapy, or other investigational agent within \< 5 times the half-life of the agent or \< 28 days (whichever is shorter) of starting study drug
• NOTE: Subjects whose immediate prior treatment was with nivolumab may start study drug 2 weeks after the last dose of nivolumab
• Symptomatic or untreated brain metastases
• Primary central nervous system (CNS) malignancy
• Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus
• Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids
• Ongoing systemic bacterial, fungal, or viral infections at Screening
• Administration of a live vaccine within 6 weeks of first dose of study drug
• Administration of any of the following within 1 week prior to the administration of study drug:
• Strong inhibitors or inducers of CYP3A4, including grapefruit products and herbal supplements
• P-glycoprotein (P-gp) inhibitors
• Warfarin, phenytoin, or other substrates of CYP2C8 or CYP2C9 with a narrow therapeutic range

Sponsors & Collaborators

• Infinity Pharmaceuticals, Inc.: lead

Study Sites (11)

UCSD

San Diego, California, 92093, United States

Location

UCLA

Santa Monica, California, 90404, United States

Location

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02116, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research and Treatment (START)

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• O'Connell BC, Hubbard C, Zizlsperger N, Fitzgerald D, Kutok JL, Varner J, Ilaria R Jr, Cobleigh MA, Juric D, Tkaczuk KHR, Elias A, Lee A, Dakhil S, Hamilton E, Soliman H, Peluso S. Eganelisib combined with immune checkpoint inhibitor therapy and chemotherapy in frontline metastatic triple-negative breast cancer triggers macrophage reprogramming, immune activation and extracellular matrix reorganization in the tumor microenvironment. J Immunother Cancer. 2024 Aug 30;12(8):e009160. doi: 10.1136/jitc-2024-009160.

  PMID: 39214650 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Triple Negative Breast Neoplasms; Adrenocortical Carcinoma; Mesothelioma

Interventions

IPI-549; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Adenoma; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Feng Chi, MD

  Infinity Pharmaceutical, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: December 22, 2015
• Study Start: December 1, 2015
• Primary Completion: January 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 4, 2022

Record last verified: 2022-04

Locations

US (11)