Advanced Solid Tumors (Part A/B/C/D)Phase 1NCT02637531
A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549
A Phase 1 study testing IPI-549 (eganelisib) and Nivolumab in people with Advanced Solid Tumors (Part A/B/C/D) and Non-small Cell Lung Cancer (Part E), run by Infinity Pharmaceuticals, Inc. at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors (Part A/B/C/D), Non-small Cell Lung Cancer (Part E), Melanoma (Part E)
- What is being tested?
- IPI-549 (eganelisib) and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 219 participants
- Where
- 11 sitesUnited States
- Study dates
- Dec 2015to Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Emory University
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02116
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Hackensack University Medical Center
Hackensack, New Jersey, 07601
MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Hematology Oncology Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952
South Texas Accelerated Research and Treatment (START)
San Antonio, Texas, 78229
UCSD
San Diego, California, 92093
UCLA
Santa Monica, California, 90404
About this study
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
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.
Read the detailed description
Study IPI-549-01 is a first-in-human multicenter, open-label, up to five-part Phase 1/1b dose-escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of IPI-549 monotherapy and IPI-549 in combination with nivolumab in subjects with advanced solid tumors.
Approximately 175 subjects will receive IPI-549, either as a monotherapy or in combination with nivolumab. Subjects will receive IPI-549 until the maximum tolerated dose (MTD) is achieved or until disease progression or unacceptable toxicity.
Part A (QD dosing) (and Part B (BID dosing) if necessary) a dose escalation part of the study will evaluate the safety and tolerability, PK, and PD of IPI-549 as a single agent in subjects with advanced solid tumors. Part A/B will determine the recommended phase 2 dose (RP2D) for IPI-549 single agent that is going to be administered in Part D as a single agent and Part C in combination with nivolumab.
Part C a dose-escalation part of the study will evaluate the safety and tolerability, PK, and PD of IPI-549 when administered in combination with IV nivolumab 240 mg every 2 weeks (Q2W) in subjects with advanced solid tumors. Part C will determine the RP2D for the combination of IPI-549 and nivolumab (combination RP2D).
Part D will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 administered as a single agent in a cohort of subjects with advanced solid tumors. Part D, Cycle 2 will also include a pilot food (a high-fat meal) effect evaluation that will have 8 subjects out of the entire cohort of subjects participating in the Part D.
Part E will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with non-small cell lung cancer (NSCLC), a cohort of subjects with melanoma and a cohort of subjects with Squamous Cell Cancer of the Head and Neck (SCCHN). One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. To be eligible for enrollment in Part E, subjects must have received an anti-PD1/PD-L1 as their most recent treatment prior to study entry. The dose level to be administered in Part E will be the combination RP2D as determined in Part C.
Part F will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with triple negative breast cancer (TNBC). One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. To be eligible for enrollment in Part E, subjects must have no prior anti-PD1/PD-L1 therapy. The dose level to be administered in Part E will be the combination RP2D as determined in Part C.
Part G will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with adrenocortical carcinoma (ACC) and a cohort of subjects with mesothelioma who have received at least first line available therapy. One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. The dose level to be administered in Part E will be the combination RP2D as determined in Part C.
Part H will evaluate the safety, tolerability, PK, and preliminary clinical activity of IPI-549 in combination with IV nivolumab 240 mg Q2W in subjects with advanced cancer with high-circulating MDSCs (ie, ≥ 20.5% as measured by Serametrix CLIA-certified assay); other indication(s) are to be determined. For subject's with a microsatellite instability-high tumor, or tumor type for which anti-PD-1/anti-PD-L1 therapy is considered standard of care, that subject must have previously received an anti-PD-1 or anti-PD-L1 therapy.
- 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)
- Being tested
- IPI-549 (eganelisib), Nivolumab
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Melanoma, Triple Negative Breast Neoplasms, Adrenocortical Carcinoma, Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IPI-549 (eganelisib)Drug
IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E)
NivolumabDrug
Also called OPDIVO
Nivolumab (240 mg, Q2W) administered intravenously (IV) in 28-day cycles (Part C/D-Annex/E).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: IPI-549 (eganelisib); Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A/B/C: Dose Limiting Toxicities (DLT)
Measured: From date of initial dose until up to 28 days for IPI-549
Part D/E: Adverse Events (AE) and safety laboratory values
Measured: 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
Measured: 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)
Measured: 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)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part A/B: Duration of response (DoR)
Measured: 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
Measured: 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 C: Plasma concentrations of IPI-549 (metabolites as appropriate)
Measured: Assessed during Days 1- 2 of Cycles 1 and 2
Part C: Overall Response Rate (ORR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part C: Duration of Response (DoR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part D: Overall Response Rate (ORR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part D: Duration of Response (DoR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part D: Progression-Free Survival (PFS)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part D: Overall Survival (OS)
Measured: Estimated to be 3 years
Part D: Plasma concentrations of IPI-549 (and metabolites, as appropriate)
Measured: Assessed during Days 1- 15 of Cycles 1 and 2, Assessed During Day 1 of Cycles 3 and 4
Part E:Overall Response Rate (ORR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part F:Overall Response Rate (ORR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part G:Overall Response Rate (ORR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part E: Duration of Response (DoR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part F: Duration of Response (DoR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part G: Duration of Response (DoR)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part E: Progression Free Survival (PFS)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part F: Progression Free Survival (PFS)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part G: Progression Free Survival (PFS)
Measured: Responses Assessed in Cycle 3 and every odd cycle through study completion, an average of 1 year
Part E: Overall Survival (OS)
Measured: Estimated to be 3 years
Part F: Overall Survival (OS)
Measured: Estimated to be 3 years
Part G: Overall Survival (OS)
Measured: Estimated to be 3 years
Part E: Plasma concentrations of IPI-549 (and metabolites, as appropriate)
Measured: Assessed during Days 1- 2 of Cycles 1 and 2
Part F: Plasma concentrations of IPI-549 (and metabolites, as appropriate)
Measured: Assessed during Days 1- 2 of Cycles 1 and 2
Part G: Plasma concentrations of IPI-549 (and metabolites, as appropriate)
Measured: Assessed during Days 1- 2 of Cycles 1 and 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionJan 2022
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid Tumors (Part A/B/C/D)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 219 participants (actual)
Sponsor and investigators
- Lead sponsor
- Infinity Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Feng Chi, MD, Study director, Infinity Pharmaceutical, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02637531
- Sponsor's protocol ID
- IPI-549-01
- Status last verified
- Apr 2022
- First submitted
- 16 Dec 2015
- Last updated
- 4 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 39214650
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02637531
- Acronym / sponsor ID
- IPI-549-01
- 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)
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 219 participants (actual)
- Lead sponsor
- Infinity Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- Jan 2022 (actual)
- Study completion
- Dec 2022 (estimated)
- First posted
- 22 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study IPI-549-01 is a first-in-human multicenter, open-label, up to five-part Phase 1/1b dose-escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of IPI-549 monotherapy and IPI-549 in combination with nivolumab in subjects with advanced solid tumors.
Approximately 175 subjects will receive IPI-549, either as a monotherapy or in combination with nivolumab. Subjects will receive IPI-549 until the maximum tolerated dose (MTD) is achieved or until disease progression or unacceptable toxicity.
Part A (QD dosing) (and Part B (BID dosing) if necessary) a dose escalation part of the study will evaluate the safety and tolerability, PK, and PD of IPI-549 as a single agent in subjects with advanced solid tumors. Part A/B will determine the recommended phase 2 dose (RP2D) for IPI-549 single agent that is going to be administered in Part D as a single agent and Part C in combination with nivolumab.
Part C a dose-escalation part of the study will evaluate the safety and tolerability, PK, and PD of IPI-549 when administered in combination with IV nivolumab 240 mg every 2 weeks (Q2W) in subjects with advanced solid tumors. Part C will determine the RP2D for the combination of IPI-549 and nivolumab (combination RP2D).
Part D will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 administered as a single agent in a cohort of subjects with advanced solid tumors. Part D, Cycle 2 will also include a pilot food (a high-fat meal) effect evaluation that will have 8 subjects out of the entire cohort of subjects participating in the Part D.
Part E will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with non-small cell lung cancer (NSCLC), a cohort of subjects with melanoma and a cohort of subjects with Squamous Cell Cancer of the Head and Neck (SCCHN). One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. To be eligible for enrollment in Part E, subjects must have received an anti-PD1/PD-L1 as their most recent treatment prior to study entry. The dose level to be administered in Part E will be the combination RP2D as determined in Part C.
Part F will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with triple negative breast cancer (TNBC). One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. To be eligible for enrollment in Part E, subjects must have no prior anti-PD1/PD-L1 therapy. The dose level to be administered in Part E will be the combination RP2D as determined in Part C.
Part G will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with adrenocortical carcinoma (ACC) and a cohort of subjects with mesothelioma who have received at least first line available therapy. One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. The dose level to be administered in Part E will be the combination RP2D as determined in Part C.
Part H will evaluate the safety, tolerability, PK, and preliminary clinical activity of IPI-549 in combination with IV nivolumab 240 mg Q2W in subjects with advanced cancer with high-circulating MDSCs (ie, ≥ 20.5% as measured by Serametrix CLIA-certified assay); other indication(s) are to be determined. For subject's with a microsatellite instability-high tumor, or tumor type for which anti-PD-1/anti-PD-L1 therapy is considered standard of care, that subject must have previously received an anti-PD-1 or anti-PD-L1 therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Part A/B: IPI-549 Dose Escalation | Experimental | Drug: IPI-549 (eganelisib)Participants receive IPI-549 orally (PO) once a day (QD) for Part A and twice a day (BID) in Part B until disease progression. |
| Part C: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants receive IPI-549 (dose determined from Part A/B) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks. |
| Part D: IPI-549 Monotherapy | Experimental | Drug: IPI-549 (eganelisib)Participants receive IPI-549 (dose determined from Part A/B) orally until disease progression. |
| Part D Annex: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks. |
| Part E: NSCLC: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants with NSCLC receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks. |
| Part E: Melanoma: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants with melanoma receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks. |
| Part E: SCCHN: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants 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. |
| Part F: TNBC: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants 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. |
| Part G: ACC: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants 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. |
| Part G: Mesothelioma: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants with mesothelioma receive IPI-549 (dose determined from Part A/B/C) orally in combination with nivolumab IV infusion (240 mg) every 2 weeks. |
| Part H: High-circulating MDSCs: IPI-549 and nivolumab | Experimental | Drug: IPI-549 (eganelisib), Drug: NivolumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- ≥ 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IPI-549 (eganelisib)IPI-549 daily dose administered orally in 28-day cycles (Part A/BC/D/D-Annex/E) | Drug | 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 |
| NivolumabAlso: OPDIVONivolumab (240 mg, Q2W) administered intravenously (IV) in 28-day cycles (Part C/D-Annex/E). | Drug | 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 |
Primary outcome
Part A/B/C: Dose Limiting Toxicities (DLT)
Time frame: From date of initial dose until up to 28 days for IPI-549
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
28 secondary outcomes
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
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
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
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
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
Part C: Plasma concentrations of IPI-549 (metabolites as appropriate)
Time frame: Assessed during Days 1- 2 of Cycles 1 and 2
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
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
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
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
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
Part D: Overall Survival (OS)
Time frame: Estimated to be 3 years
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
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
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
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
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
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
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
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
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
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
Part E: Overall Survival (OS)
Time frame: Estimated to be 3 years
Part F: Overall Survival (OS)
Time frame: Estimated to be 3 years
Part G: Overall Survival (OS)
Time frame: Estimated to be 3 years
Part E: Plasma concentrations of IPI-549 (and metabolites, as appropriate)
Time frame: Assessed during Days 1- 2 of Cycles 1 and 2
Part F: Plasma concentrations of IPI-549 (and metabolites, as appropriate)
Time frame: Assessed during Days 1- 2 of Cycles 1 and 2
Part G: Plasma concentrations of IPI-549 (and metabolites, as appropriate)
Time frame: Assessed during Days 1- 2 of Cycles 1 and 2
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2022.
- Derived from this study: PubMed 39214650O'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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Feng Chi, MD study director
Infinity Pharmaceutical, Inc.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IPI-549 (eganelisib) and Nivolumab in people with Advanced Solid Tumors (Part A/B/C/D) and Non-small Cell Lung Cancer (Part E), run by Infinity Pharmaceuticals, Inc. at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A/B/C: Dose Limiting Toxicities (DLT) (time frame: From date of initial dose until up to 28 days for IPI-549). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02637531, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2022.