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SAN FRANCISCO—Preliminary results of a phase 1 trial suggest the PI3K-delta/gamma inhibitor IPI-145 is active in patients with relapsed or refractory T-cell lymphomas.
Among 26 evaluable patients, 9 experienced partial responses to treatment with IPI-145, and 1 achieved a complete response, for an overall response rate (ORR) of 38%.
The drug also appeared to be well-tolerated, although 30% of patients did experience treatment-related severe adverse events.
Steven Horwitz, MD, of Memorial Sloan-Kettering Cancer Center in New York, and his colleagues presented these results in a poster at the 6th Annual T-cell Lymphoma Forum, which took place January 23-25.
The study was sponsored by Infinity Pharmaceuticals, Inc., the company developing IPI-145.
Patient and treatment characteristics
The trial included 30 patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Of the 17 CTCL patients, 16 had mycosis fungoides or Sezary syndrome, and 1 had primary cutaneous anaplastic large-cell lymphoma (ALCL).
Of the 13 patients with PTCL, 3 had angioimmunoblastic T-cell lymphoma (AITL), 3 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL), 3 had PTCL-not otherwise specified, 2 had ALCL, 1 had enteropathy-associated T-cell lymphoma (EATL), and 1 had NK T-cell lymphoma (NKTL).
The patients had advanced disease, with a median of 5 prior systemic therapies (range, 1-11) and a median of 1 month from their last therapy to the first dose on study (range, 0.2-12).
Patients received IPI-145 in escalating doses, from 25 mg to 100 mg twice daily (n=10) and in an expansion cohort at 75 mg twice daily (n=20). All 30 patients were evaluable for the safety analysis, but only 26 were evaluable for clinical activity.
Response by disease type
The ORR for all 26 patients was 38% (1 complete and 9 partial responses).
Among the 11 evaluable PTCL patients, the ORR was 55%. One patient had a complete response, and 5 had partial responses.
Of the 15 evaluable CTCL patients, 4 had partial responses, for an ORR of 27%. In addition, 7 CTCL patients had stable disease.
The median time to response was 1.9 months (range, 1.5-2.7) for patients with PTCL and 2.4 months (range, 1.7-3.8) for patients with CTCL.
Four patients with PTCL and 3 patients with CTCL remain on treatment.
Adverse events
IPI-145 was generally well-tolerated, according to the researchers.
The most common adverse events of any grade were an increases in ALT/AST (47%), fatigue (37%), pyrexia (33%), diarrhea (30%), cough (27%), headache (27%), nausea (27%), rash (23%), increases in alkaline phosphatase (20%), increases in blood creatinine (17%), and weight loss (17%).
Grade 3 side effects included increased ALT/AST (33%), rash (13%), and fatigue (10%). One patient (3%) had grade 4 ALT/AST increases.
Forty percent of patients had severe adverse events, and 30% were treatment-related. Among CTCL patients, the severe events included ALT/AST increases (n=1), pneumonitis (n=1), HSV pneumonitis (n=1), lung infection (n=1), pyrexia (n=1), and staphylococcal sepsis (n=1).
Among PTCL patients, severe events included diarrhea (n=2), pneumonia (n=2), vomiting (n=2), cellulitis (n=1), colitis (n=1), dehydration (n=1), hypotension (n=1), pneumonia cytomegaloviral (n=1), pyrexia (n=1), and rash (macular papular; n=1).
Six CTCL patients and 3 PTCL patients discontinued treatment due to adverse events.
Pharmacodynamics
The data showed that treatment with IPI-145 led to decreases in serum levels of cytokines and chemokines known to play important roles in lymphocyte trafficking and function.
The researchers said this further supports the rationale that inhibiting PI3K-delta and PI3K-gamma has the potential to provide a therapeutic benefit for T-cell lymphomas and other hematologic malignancies.
For more details on this research, see the poster on Infinity’s website: http://www.infi.com/product-candidates-publications.asp. 
SAN FRANCISCO—Preliminary results of a phase 1 trial suggest the PI3K-delta/gamma inhibitor IPI-145 is active in patients with relapsed or refractory T-cell lymphomas.
Among 26 evaluable patients, 9 experienced partial responses to treatment with IPI-145, and 1 achieved a complete response, for an overall response rate (ORR) of 38%.
The drug also appeared to be well-tolerated, although 30% of patients did experience treatment-related severe adverse events.
Steven Horwitz, MD, of Memorial Sloan-Kettering Cancer Center in New York, and his colleagues presented these results in a poster at the 6th Annual T-cell Lymphoma Forum, which took place January 23-25.
The study was sponsored by Infinity Pharmaceuticals, Inc., the company developing IPI-145.
Patient and treatment characteristics
The trial included 30 patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Of the 17 CTCL patients, 16 had mycosis fungoides or Sezary syndrome, and 1 had primary cutaneous anaplastic large-cell lymphoma (ALCL).
Of the 13 patients with PTCL, 3 had angioimmunoblastic T-cell lymphoma (AITL), 3 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL), 3 had PTCL-not otherwise specified, 2 had ALCL, 1 had enteropathy-associated T-cell lymphoma (EATL), and 1 had NK T-cell lymphoma (NKTL).
The patients had advanced disease, with a median of 5 prior systemic therapies (range, 1-11) and a median of 1 month from their last therapy to the first dose on study (range, 0.2-12).
Patients received IPI-145 in escalating doses, from 25 mg to 100 mg twice daily (n=10) and in an expansion cohort at 75 mg twice daily (n=20). All 30 patients were evaluable for the safety analysis, but only 26 were evaluable for clinical activity.
Response by disease type
The ORR for all 26 patients was 38% (1 complete and 9 partial responses).
Among the 11 evaluable PTCL patients, the ORR was 55%. One patient had a complete response, and 5 had partial responses.
Of the 15 evaluable CTCL patients, 4 had partial responses, for an ORR of 27%. In addition, 7 CTCL patients had stable disease.
The median time to response was 1.9 months (range, 1.5-2.7) for patients with PTCL and 2.4 months (range, 1.7-3.8) for patients with CTCL.
Four patients with PTCL and 3 patients with CTCL remain on treatment.
Adverse events
IPI-145 was generally well-tolerated, according to the researchers.
The most common adverse events of any grade were an increases in ALT/AST (47%), fatigue (37%), pyrexia (33%), diarrhea (30%), cough (27%), headache (27%), nausea (27%), rash (23%), increases in alkaline phosphatase (20%), increases in blood creatinine (17%), and weight loss (17%).
Grade 3 side effects included increased ALT/AST (33%), rash (13%), and fatigue (10%). One patient (3%) had grade 4 ALT/AST increases.
Forty percent of patients had severe adverse events, and 30% were treatment-related. Among CTCL patients, the severe events included ALT/AST increases (n=1), pneumonitis (n=1), HSV pneumonitis (n=1), lung infection (n=1), pyrexia (n=1), and staphylococcal sepsis (n=1).
Among PTCL patients, severe events included diarrhea (n=2), pneumonia (n=2), vomiting (n=2), cellulitis (n=1), colitis (n=1), dehydration (n=1), hypotension (n=1), pneumonia cytomegaloviral (n=1), pyrexia (n=1), and rash (macular papular; n=1).
Six CTCL patients and 3 PTCL patients discontinued treatment due to adverse events.
Pharmacodynamics
The data showed that treatment with IPI-145 led to decreases in serum levels of cytokines and chemokines known to play important roles in lymphocyte trafficking and function.
The researchers said this further supports the rationale that inhibiting PI3K-delta and PI3K-gamma has the potential to provide a therapeutic benefit for T-cell lymphomas and other hematologic malignancies.
For more details on this research, see the poster on Infinity’s website: http://www.infi.com/product-candidates-publications.asp.
SAN FRANCISCO—Preliminary results of a phase 1 trial suggest the PI3K-delta/gamma inhibitor IPI-145 is active in patients with relapsed or refractory T-cell lymphomas.
Among 26 evaluable patients, 9 experienced partial responses to treatment with IPI-145, and 1 achieved a complete response, for an overall response rate (ORR) of 38%.
The drug also appeared to be well-tolerated, although 30% of patients did experience treatment-related severe adverse events.
Steven Horwitz, MD, of Memorial Sloan-Kettering Cancer Center in New York, and his colleagues presented these results in a poster at the 6th Annual T-cell Lymphoma Forum, which took place January 23-25.
The study was sponsored by Infinity Pharmaceuticals, Inc., the company developing IPI-145.
Patient and treatment characteristics
The trial included 30 patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Of the 17 CTCL patients, 16 had mycosis fungoides or Sezary syndrome, and 1 had primary cutaneous anaplastic large-cell lymphoma (ALCL).
Of the 13 patients with PTCL, 3 had angioimmunoblastic T-cell lymphoma (AITL), 3 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL), 3 had PTCL-not otherwise specified, 2 had ALCL, 1 had enteropathy-associated T-cell lymphoma (EATL), and 1 had NK T-cell lymphoma (NKTL).
The patients had advanced disease, with a median of 5 prior systemic therapies (range, 1-11) and a median of 1 month from their last therapy to the first dose on study (range, 0.2-12).
Patients received IPI-145 in escalating doses, from 25 mg to 100 mg twice daily (n=10) and in an expansion cohort at 75 mg twice daily (n=20). All 30 patients were evaluable for the safety analysis, but only 26 were evaluable for clinical activity.
Response by disease type
The ORR for all 26 patients was 38% (1 complete and 9 partial responses).
Among the 11 evaluable PTCL patients, the ORR was 55%. One patient had a complete response, and 5 had partial responses.
Of the 15 evaluable CTCL patients, 4 had partial responses, for an ORR of 27%. In addition, 7 CTCL patients had stable disease.
The median time to response was 1.9 months (range, 1.5-2.7) for patients with PTCL and 2.4 months (range, 1.7-3.8) for patients with CTCL.
Four patients with PTCL and 3 patients with CTCL remain on treatment.
Adverse events
IPI-145 was generally well-tolerated, according to the researchers.
The most common adverse events of any grade were an increases in ALT/AST (47%), fatigue (37%), pyrexia (33%), diarrhea (30%), cough (27%), headache (27%), nausea (27%), rash (23%), increases in alkaline phosphatase (20%), increases in blood creatinine (17%), and weight loss (17%).
Grade 3 side effects included increased ALT/AST (33%), rash (13%), and fatigue (10%). One patient (3%) had grade 4 ALT/AST increases.
Forty percent of patients had severe adverse events, and 30% were treatment-related. Among CTCL patients, the severe events included ALT/AST increases (n=1), pneumonitis (n=1), HSV pneumonitis (n=1), lung infection (n=1), pyrexia (n=1), and staphylococcal sepsis (n=1).
Among PTCL patients, severe events included diarrhea (n=2), pneumonia (n=2), vomiting (n=2), cellulitis (n=1), colitis (n=1), dehydration (n=1), hypotension (n=1), pneumonia cytomegaloviral (n=1), pyrexia (n=1), and rash (macular papular; n=1).
Six CTCL patients and 3 PTCL patients discontinued treatment due to adverse events.
Pharmacodynamics
The data showed that treatment with IPI-145 led to decreases in serum levels of cytokines and chemokines known to play important roles in lymphocyte trafficking and function.
The researchers said this further supports the rationale that inhibiting PI3K-delta and PI3K-gamma has the potential to provide a therapeutic benefit for T-cell lymphomas and other hematologic malignancies.
For more details on this research, see the poster on Infinity’s website: http://www.infi.com/product-candidates-publications.asp.