Study iPi-145-06 is a Phase 2, open-label, single arm safety and efficacy study of iPi-145 administered orally to subjects diagnosed with inHL (FL, MZL, or SLL) whose disease is refractory to rituximab and chemotherapy in combination or RiT.
Schedule of administration
Subjects will receive a starting dose of 25 mg iPi-145 BiD over the course of 28-day treatment cycles for up to 13 cycles.
after completing 13 treatment cycles of iPi-145, subjects who have documented evidence of
response (CR or PR) at the Cycle 14 Day 1 response assessment according to the revised iWG criteria1 may continue to receive additional cycles of iPi-145 for an additional year for a total of 2 years of treatment.
overall Response Rate (oRR), with overall response defined as best response of complete response/remission (CR) or partial response/remission (PR), according to the revised international Working Group (iWG) Criteria.
* Treatment-emergent adverse events (Teaes), eCG
measures, and changes in safety laboratory values
* Duration of response (DoR), defined as the time
from the first documentation of response to the first documentation of progressive disease (PD) or death due to any cause
* Progression-free survival (PFS), defined as the time from the first dose of study treatment to the first
documentation of PD or death due to any cause
* overall survival (oS) defined as the time from the
first dose of study treatment to the date of death
* Time to response (TTR), defined as the time from the
first dose of study treatment to the first
documentation of response (complete or partial)
* PK parameters derived from plasma iPi-145
concentrations and, if applicable, its metabolite(s)
* Serum, plasma and tissue biomarkers and blood
* Germline Dna sequence variations
* Tumor genomic features (e.g. Dna sequence
variation, Dna copy number variation, and/or Rna
* Health-related QoL of subjects as assessed by the
following subject-reported questionnaire:
o euroQol-5D (eQ-5D), a standardized
instrument for use as a measure of health-
Subjects are eligible for inclusion in the study if they meet
the following criteria:
1. Age 18 years or older.
2. Subjects who have been diagnosed with indolent NHL
[defined as FL, MZL (splenic, nodal and extranodal), or
SLL] that has progressed.
a. For subjects for whom the most recent biopsy was
performed >36 months before the first dose of
IPI-145, a repeat biopsy to confirm histology
should be performed, unless medically
b. For subjects who progressed within 2 months of
initiating last prior chemotherapy, a repeat biopsy
to confirm histology should be performed, unless
3. Subjects must have disease that is refractory to a
chemotherapy induction regimen or RIT. The
chemotherapy induction regimen (with or without
rituximab) must contain at least one alkylating agent or
purine nucleoside antagonist. See Appendix 5 for
examples of suitable prior chemotherapy.
Refractory is defined as either:
a. Lack of a CR or PR while receiving the
chemotherapy induction regimen or RIT
b. PD within 6 months of the last dose of the
chemotherapy induction regimen or RIT
documented by computed tomography (CT),
PET/CT or MRI obtained within 6 months after the
Note: Subjects exhibiting clinical progression within 6 months after the last dose of a chemotherapy induction regimen or RIT who are unable to undergo CT, PET/CT
or MRI scans within the 6 month timeframe are allowed
up to an additional 30 days to confirm radiologic
4. Subjects must have disease that is refractory to
rituximab. Refractory is defined as any of the following:
a. Lack of a CR or PR during treatment with a full
course of single-agent rituximab (>=4 doses of
375 mg/m2, weekly) or >=2 doses of >=375 mg/m2 of rituximab in combination with chemotherapy
b. PD within 6 months of the last dose of a full
course of single-agent rituximab or rituximab in
combination with chemotherapy
c. PD during, or within 6 months of the last dose of
rituximab maintenance therapy
5. Measurable disease with a lymph node or tumor mass
>=1.5 cm in at least one dimension by CT, PET/CT or
6. Eastern Cooperative Oncology Group (ECOG)
performance status 0-2 (corresponds to Karnofsky
Performance Status [KPS] >=60%).
7. Adequate renal function, defined as serum creatinine <=2
x upper limit of normal (ULN).
8. Adequate hepatic function, defined as total bilirubin <=1.5
x ULN (unless elevated due to Gilbert[Single Quote]s syndrome) and aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels <=3 x ULN.
9. Negative serum or urine [BETA] human chorionic gonadotropin ([BETA]hCG) pregnancy test within 1 week before first dose of study drug if the subject is a woman of childbearing
potential (WCBP) (defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least
24 consecutive months for women <=55 years or 12
consecutive months for women >55 years).
10. Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of
the study, including 30 days after the last dose of
IPI-145. Sexually active men, and women using oral
contraceptive pills, should also use barrier contraception.
11. Ability to adhere to the study visit schedule and all
12. Signed and dated institutional review board
(IRB)/independent ethics committee (IEC)-approved
informed consent form before any study specific-
screening procedures are performed.