Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Idelalisib
Zydelig · 11 trials · 17 indications
PFS was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. PFS (months) = (minimum (date of disease progression, date of death) - date of randomization + 1)/30.4375.
Progression-free survival was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression was CLL progression based on standard criteria (other than lymphocytosis alone) as defined by the 2008 update of the International Workshop on CLL guidelines, ie, appearance of any new lesion; increase by ≥ 50% in the sum of the products of the perpendicular diameters of measured lymph nodes (SPD); new or ≥ 50% enlargement of liver or spleen; transformation to a more aggressive histology (eg, Richter's or prolymphocytic transformation); reduction in the number of blood cells (cytopenia) attributable to CLL.
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on IWCLL 2008 criteria.
The proportion of patients who discontinued the study due to Zydelig-related adverse events.
Overall response rate (ORR) was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as assessed by the investigator. * CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. * PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions.
An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug.
An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug.
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. If the relevant baseline laboratory value was missing, then any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment-emergent.The most severe graded abnormality from all tests was counted for each participant. Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening.
An AE was any untoward medical occurrence in a clinical study participant which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: 1) Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug; and/or 2) Any AEs leading to premature discontinuation of study drug.
Lower limit of quantitation was 5 ng/mL for idelalisib and metabolite GS-563117 both.
The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).
Participants were assessed for clinical response by appropriate imaging at the end of cycles 3, 6, 9, and 12. Overall response rate (ORR) was assessed based on standardized criteria (Cheson 2007), and was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) based on investigator assessment after the start of idelalisib treatment until progression or the end of study drug treatment. * CR was defined as the disappearance of all evidence of disease. * PR was defined the regression of measurable disease and no new sites.
Duration of exposure to IDELA was summarized using descriptive statistics.
Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02
| Arm | Type | Description |
|---|---|---|
| Idelalisib+bendamustine+rituximab | EXPERIMENTAL | Participants will receive idelalisib plus bendamustine and rituximab |
| Placebo to match idelalisib+bendamustine+rituximab | PLACEBO_COMPARATOR | Participants will receive placebo to match idelalisib plus bendamustine and rituximab |
| Idelalisib + rituximab | ACTIVE_COMPARATOR | Participants will receive idelalisib plus rituximab |
| Placebo + rituximab | PLACEBO_COMPARATOR | Participants will receive placebo to match idelalisib plus rituximab |
| Idelalisib & Ofatumumab | EXPERIMENTAL | Idelalisib will be given orally continuously at 150 mg BID. On day 57, ofatumumab will begin with the 300 mg dose, given after idelalisib is taken. Ofatumumab will then be administered at 1000 mg weekly to complete 8 weeks (days 64, 71, 78, 85, 92, 99, 106) throughout Cycles 3 and 4. This will be followed by monthly ofatumumab on weeks 20, 24, 28, 32 to complete 4 additional cycles (5-8). The overall induction treatment period will then be 8 months, comprised of two months of single agent idelalisib followed by 6 months of ofatumumab with idelalisib. After the completion of the induction treatment, idelalisib will continue indefinitely in arbitrarily defined 28 day cycles in all participants who have not had excessive toxicity and do not have progressive disease. |
| Oral Zydelig 150 mg BID | EXPERIMENTAL | Zydelig given orally at 150 mg twice daily continuously on 28-day cycles starting 30 to 120 days after autologous stem cell transplantation for patients with indolent or transformed indolent B-cell NHL, for up to 1 year maintenance duration. Dose withhold/modification is allowed according to tolerability/toxicity. |
| Idelalisib | EXPERIMENTAL | Participants will receive up to 300 mg of idelalisib twice daily. |
| lenalidomide (Phase II) | ACTIVE_COMPARATOR | Lenalidomide will be administered orally at 20 mg daily on days 1-21, repeated every 28 days for a maximum of 12 cycles (48 weeks). (Phase II) |
| lenalidomide and idelalisib (Phase II) | EXPERIMENTAL | Lenalidomide will be administered orally and daily on days 1-21, repeated every 28 days for a maximum of 12 cycles (48 weeks). Idelalisib will be orally administered for continuous 28-day cycles until progression, intolerance, or patient/physician discretion. Dosing will be determined by the Phase I portion of the study. (Phase II) |
| lenalidomide and idelalisib | EXPERIMENTAL | Lenalidomide: Lenalidomide will be administered orally on days 1-21 followed by 7 days of rest, every 28 days. A treatment cycle will be considered 28 days in length. In the absence of intolerable toxicity or disease progression, lenalidomide will be given for a total of 12 cycles. Idelalisib: Dosing is fixed in all cohorts receiving idelalisib at 150 mg orally (twice daily) for 12 cycles, with the exception of dose modifications for toxicity. |
| Idelalisib + Rituximab + Bendamustine | EXPERIMENTAL | Participants with CLL, iNHL and mantle cell lymphoma (MCL) will receive treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m\^2 IV on Days 1 \& 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m\^2 IV on Days 1 \& 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m\^2 IV on Days 1 \& 2 of each 28-day cycle, Cycles 1 - 6 |
| Idelalisib + Bendamustine | EXPERIMENTAL | Participants with CLL and iNHL will receive treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m\^2 IV on Days 1 \& 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m\^2 IV on Days 1 \& 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m\^2 IV on Days 1 \& 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m\^2 IV on Days 1 \& 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m\^2 IV on Days 1 \& 2 of each 28-day cycle, Cycles 1 - 6 |
| Idelalisib + Ofatumumab | EXPERIMENTAL | Participants with CLL will receive treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) |
| Idelalisib + Fludarabine | EXPERIMENTAL | Participants with CLL will receive treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m\^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 |
| Idelalisib + Everolimus | EXPERIMENTAL | Participants with MCL will receive treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle |
| Idelalisib + Bortezomib | EXPERIMENTAL | Participants with MCL will receive treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m\^2 subcutaneously on Days 1, 8 \& 15 of each 28-day cycle |
| Idelalisib + Chlorambucil | EXPERIMENTAL | Participants with CLL will receive treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m\^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 |
| Idelalisib + Rituximab + Chlorambucil | EXPERIMENTAL | Participants with CLL will receive treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m\^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m\^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 |
| Idelalisib + Rituximab + Lenalidomide | EXPERIMENTAL | Participants with CLL and iNHL will receive treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) \& Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m\^2 IV on Days 1 \& 8 of Cycle 1 \& Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) \& Days 1 - 21 of next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) \& Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m\^2 IV on Days 1 \& 8 of Cycle 1 \& Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) \& Days 1 - 21 of next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) \& Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m\^2 IV on Days 1 \& 8 of Cycle 1 \& Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) \& Days 1 - 21 of next five 28-day cycles |
| Name | Type | Description |
|---|---|---|
| Idelalisib | DRUG | Idelalisib 150 mg administered orally twice daily |
| Rituximab | DRUG | Rituximab 375 mg/m\^2 on Day 1, then 500 mg/m\^2 every 28 days administered intravenously for a maximum of 6 infusions |
| Bendamustine | DRUG | Bendamustine 70 mg/mg\^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions |
| Placebo to match idelalisib | DRUG | Placebo to match idelalisib administered orally twice daily |
| Ofatumumab | DRUG | Ofatumumab will then be administered at 1000 mg weekly to complete 8 weeks (days 64, 71, 78, 85, 92, 99, 106) throughout Cycles 3 and 4. This will be followed by monthly ofatumumab on weeks 20, 24, 28, 32 to complete 4 additional cycles (5-8). |
| Zydelig | DRUG | Zydelig given at 150mg continuously in 28-day cycles |
| lenalidomide | DRUG | given PO |
| Fludarabine | DRUG | Fludarabine administered orally |
| Everolimus | DRUG | Everolimus administered orally twice daily until disease progression |
| Bortezomib | DRUG | Bortezomib administered as a subcutaneous injection |
| Chlorambucil | DRUG | Chlorambucil administered on Days 1-7 every 28 days to allow appropriate therapy for participants with CLL and to coordinate into a cycle period equivalent to other study treatment regimens. |
Key Inclusion Criteria: * Previously treated recurrent CLL * Measurable lymphadenopathy * Requires therapy for CLL * Has experienced CLL progression \< 36 months since the completion of the last prior therapy Key Exclusion Criteria: * Recent history of a major non-CLL malignancy * Evidence of an ...
Zydelig is being studied as maintenance therapy in B-cell Non Hodgkin Lymphoma after autologous stem cell transplantation. The Phase 2 trial enrolled patients with several B-cell lymphoma subtypes, including follicular lymphoma, marginal zone lymphoma, Waldenstrom macroglobulinemia, small lymphocytic lymphoma, and transformed lymphoma.
Zydelig is developed by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. Gilead is the sponsor responsible for the clinical development program for Zydelig in B-cell Non Hodgkin Lymphoma.
Zydelig is in Phase 2 development for Non Hodgkin Lymphoma. The recorded trial is a completed Phase 2 study, and Zydelig is investigational in this setting rather than an approved treatment for this indication.
Zydelig has been evaluated in the Phase 2 trial NCT03133221, titled 1630GCC: Zydelig Maintenance in B-Cell Non-Hodgkin's Lymphoma After Autologous Stem Cell Transplantation. That study is completed, enrolled 17 participants, and was conducted in the United States.
The Phase 2 trial NCT03133221 was an uncontrolled, open-label study, not randomized and not double blinded. It enrolled 17 adults aged 18 years and older of all sexes, and it did not select patients by biomarker. Participants had B-cell Non Hodgkin Lymphoma and received Zydelig as maintenance after autologous stem cell transplantation.