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Trial record 1 of 1 for:    NCT02637531
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A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549

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ClinicalTrials.gov Identifier: NCT02637531
Recruitment Status : Recruiting
First Posted : December 22, 2015
Last Update Posted : September 12, 2018
Sponsor:
Information provided by (Responsible Party):
Infinity Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
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) Drug: IPI-549 Drug: Nivolumab Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/1b First-In-Human, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549 Monotherapy and in Combination With Nivolumab in Subjects With Advanced Solid Tumors
Study Start Date : December 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : September 2019


Arm Intervention/treatment
Experimental: Part A/B: IPI-549 Dose Escalation
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
IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E)

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

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

Experimental: Part D: IPI-549 Monotherapy
Participants receive IPI-549 (dose determined from Part A/B) orally until disease progression.
Drug: IPI-549
IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E)

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

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

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

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

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

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

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

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

Experimental: Part F: TNBC: IPI-549 and nivolumab
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
IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E)

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

Experimental: Part G: ACC: IPI-549 and nivolumab
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
IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E)

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

Experimental: Part G: Mesothelioma: IPI-549 and nivolumab
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
IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E)

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

Experimental: Part H: High-circulating MDSCs: IPI-549 and nivolumab
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
IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E)

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




Primary Outcome Measures :
  1. Part A/B/C: Dose Limiting Toxicities (DLT) [ Time Frame: From date of initial dose until up to 28 days for IPI-549 ]
  2. Part D/E: Adverse Events (AE) and safety laboratory values [ Time Frame: 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 Outcome Measures :
  1. Part A/B: Adverse Events (AE) and safety laboratory values [ Time Frame: 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 ]
  2. Part A/B: Plasma concentrations of IPI-549 (metabolites, as appropriate) [ Time Frame: Assessed during Days 1- 22 of Cycles 1 and 2, Assessed During Day 1 of Cycles 3 and 4 ]
  3. Part A/B: Overall response rate (ORR), complete response/remission (CR) or partial response/remission (PR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  4. Part A/B: Duration of response (DoR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  5. Part C: Adverse Events (AE) and safety laboratory values [ Time Frame: 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 ]
  6. Part C: Plasma concentrations of IPI-549 (metabolites as appropriate) [ Time Frame: Assessed during Days 1- 2 of Cycles 1 and 2 ]
  7. Part C: Overall Response Rate (ORR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  8. Part C: Duration of Response (DoR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  9. Part D: Overall Response Rate (ORR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  10. Part D: Duration of Response (DoR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  11. Part D: Progression-Free Survival (PFS) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  12. Part D: Overall Survival (OS) [ Time Frame: Estimated to be 3 years ]
  13. Part D: Plasma concentrations of IPI-549 (and metabolites, as appropriate) [ Time Frame: Assessed during Days 1- 15 of Cycles 1 and 2, Assessed During Day 1 of Cycles 3 and 4 ]
  14. Part E:Overall Response Rate (ORR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  15. Part F:Overall Response Rate (ORR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  16. Part G:Overall Response Rate (ORR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  17. Part E: Duration of Response (DoR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  18. Part F: Duration of Response (DoR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  19. Part G: Duration of Response (DoR) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  20. Part E: Progression Free Survival (PFS) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  21. Part F: Progression Free Survival (PFS) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  22. Part G: Progression Free Survival (PFS) [ Time Frame: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year ]
  23. Part E: Overall Survival (OS) [ Time Frame: Estimated to be 3 years ]
  24. Part F: Overall Survival (OS) [ Time Frame: Estimated to be 3 years ]
  25. Part G: Overall Survival (OS) [ Time Frame: Estimated to be 3 years ]
  26. Part E: Plasma concentrations of IPI-549 (and metabolites, as appropriate) [ Time Frame: Assessed during Days 1- 2 of Cycles 1 and 2 ]
  27. Part F: Plasma concentrations of IPI-549 (and metabolites, as appropriate) [ Time Frame: Assessed during Days 1- 2 of Cycles 1 and 2 ]
  28. Part G: Plasma concentrations of IPI-549 (and metabolites, as appropriate) [ Time Frame: Assessed during Days 1- 2 of Cycles 1 and 2 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All subjects must meet the following criteria for inclusion:

  • ≥ 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
  • Failure to respond to standard therapy, or for whom no appropriate therapies are available (based on the judgment of the Investigator The most recent treatment prior to study entry must be an anti-PD-1 or anti-PD-L1 antibody given as either monotherapy or in combination
  • Subjects with NSCLC Tumors that harbor an actionable genetic alteration for which there is a corresponding approved therapy for that specific alteration (including but not limited to alterations in EGFR, ALK, and ROS) must have progressed on, or had intolerance to, the respective therapy

Subjects entering Part F must also meet the following additional criteria:

  • Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing, based on last available tumor tissue; or another tumor type to be determined

    • ER/PgR negativity to follow local guidelines
    • If IHC HER2 2+, a negative FISH test is required
    • Inflammatory triple negative breast cancer is allowed
  • Must have received and failed/progressed a cytotoxic chemotherapy as first line therapy per standard of care
  • No prior anti-PD-1 or anti-PD-L1 therapy

Subjects entering Part G must also meet the following additional criteria:

  • Histological or cytological evidence of ACC, mesothelioma, or another tumor type to be determined

    • Both pleural and peritoneal mesothelioma are allowed
    • Epithelioid, sarcomatoid, or biphasic mesothelioma subtypes are allowed
  • Progression after at least first line available therapy

Patients entering Part H must also meet the following additional criteria:

High-circulating MDSCs, currently defined for this study as MDSCs

≥ 20.5% as measured by CLIA-certified Serametrix assay Microsatellite status of tumor has been determined Patients with tumors that are microsatellite instability-high must have previously received an anti-PD-1/anti-PD-L1 therapy and progressed on therapy If patient's tumor type is one for which anti-PD-1/anti-PD-L1 therapy is standard of care, patient must have previously received an anti-PD-1 or anti-PD-L1 therapy and progressed while on that therapy

Exclusion Criteria:

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

NOTE: Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met

  • 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
    • Medications associated with QTc interval prolongation or Torsades de Pointes
  • Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of triplicate readings) NOTE: criterion does not apply to subjects with a right or left bundle branch block
  • Parts C, D-Annex, and E only: Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
  • Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or prostate intraepithelial neoplasia
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
  • History of peptic ulcer and/or gastrointestinal bleed
  • History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening
  • Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the subject associated with his or her participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02637531


Contacts
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Contact: Jennifer Roberts 617-453-1298 IPI-549-01@infi.com

Locations
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United States, California
UCSD Recruiting
San Diego, California, United States, 92093
UCLA Recruiting
Santa Monica, California, United States, 90404
United States, Florida
Hematology Oncology Associates of the Treasure Coast Recruiting
Port Saint Lucie, Florida, United States, 34952
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02116
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
South Texas Accelerated Research and Treatment (START) Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Infinity Pharmaceuticals, Inc.
Investigators
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Study Director: Sam Agresta, MD Infinity Pharmaceutical, Inc.

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Responsible Party: Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02637531     History of Changes
Other Study ID Numbers: IPI-549-01
First Posted: December 22, 2015    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 2018

Keywords provided by Infinity Pharmaceuticals, Inc.:
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)

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Melanoma
Mesothelioma
Triple Negative Breast Neoplasms
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Adrenocortical Carcinoma
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
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms, Mesothelial
Breast Neoplasms
Breast Diseases
Skin Diseases
Carcinoma