Unresectable Melanoma
Conditions
Keywords
Anti-PD-1 monoclonal antibody (mAb)
Brief summary
This trial is a Phase I/II study in which a combination of duvelisib and nivolumab will be used to treat a total of patients diagnosed with advanced unresectable melanoma who have progressed on anti-PD1 therapy. The Recommended Phase II Dose of oral duvelisib will be determined and administered with intravenous nivolumab 480mg for up to 1 year or until the patient's disease does not progress or the patient experiences unacceptable side effects to treatment.
Detailed description
This trial will study of PI3Kγδ inhibitor duvelisib in combination with nivolumab in patients with advanced unresectable melanoma who have progressed on anti-PD1 therapy. In the Phase I part of the study (18) patients will be administered nivolumab 480mg intravenously and duvelisib orally in doses from 15mg once a day to 25mg twice a day to determine the recommended dose for the Phase II part of the study. In the Phase II study patients will be administered nivolumab 480mg intravenously and duvelisib orally (dose not determined until the Phase 1 study is completed) up to 1 year as long as their disease doesn't progress or have unacceptable side effects to the study drugs. This trial will attempt to determine whether duvelisib acts as an immunomodulator, to shift the TME from an immunosuppressive to an immunostimulatory setting, to overcome acquired resistance in anti-PD1 treated patients. The phase I portion of the study is uniquely designed to find the ideal dose of duvelisib as an immunomodulator, which is suspected to be lower than the previously determined maximum tolerated dose (MTD) of duvelisib in lymphoma studies.
Interventions
DRUGNivolumab
Nivolumab is a human IgG4 monoclonal antibody that blocks PD-1. It is a type of immunotherapy and works as a checkpoint inhibitor, blocking a signal that prevents activation of T cells from attacking the cancer.
DRUGDuvelisib
Duvelisib is a potent inhibitor of both γ and δ isoforms. Duvelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Sponsors
Secura Bio, Inc.
Bristol-Myers Squibb
John Kirkwood
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* AJCC 8th edition criteria for unresectable stage IIIB, stage IIIC, stage IIID or stage IV melanoma who have received at least 3 months of prior treatment with an anti-PD1 or anti-PDL1 antibody and who have progressed on this treatment. Patients who have received a combination anti-PD1 and anti-CTLA4 therapy who exhibit progression at this interval are also permitted. There are no restrictions regarding time since last anti-PD1 treatment, or number of therapies after anti-PD1. * Age ≥ 18 years * ECOG performance status ≤ 2 or Karnofsky ≥ 60% * Patients must have normal organ and bone marrow function as defined below: * Hemoglobin ≥9.0 g/dL * Absolute neutrophil count ≥1500 cells/µL * Platelets ≥100,000 cells/µL * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). Patients with Gilbert's syndrome must have normal direct bilirubin * AST/ALT ≤2.5x ULN in subjects with liver metastasis, must be within normal limits for those without liver metastasis * Creatinine \< 1.5 mg/dL * For patients with actionable BRAF mutations, treatment with BRAF and MEK inhibitors prior to initiation on trial is recommended, unless patients are intolerant of therapy or choose not to pursue BRAF targeted therapy. * Patients must have measurable disease, defined as at least one tumor lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥10mm with CT scan, MRI or by calipers if documented on clinical exam. If patients have a single lesion, the lesion must be amenable to biopsy without interfering with radiographic assessment as determined by one of the co-PIs. * Duvelisib and nivolumab therapy may be harmful for a developing fetus. Women of child bearing potential (WCBP) must have a negative urine or serum β human chorionic gonadotropin (βhCG) pregnancy test within 7 days before starting treatment. WCBP and men must agree to use highly effective contraception (pharmacologic birth control, barrier methods or abstinence) prior to study entry and for the duration of study participation through 5 months after the last dose of study medication. Should a woman become pregnant while she or her partner are participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use highly effective contraception prior to the study, for the duration of study participation and 12 weeks following the last dose. * WCBP defined as a sexually mature woman who as not undergone surgical sterilization or who has not been naturally postmenopausal for at least 12 consecutive months for women \>55 years of age * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Patients with known or suspected CNS metastases with are excluded, unless the following criteria are met: * Subjects have controlled brain metastasis, defined as metastases without radiographic progression for at least 4 weeks following treatment with stereotactic radiation and/or surgical treatment at the time of randomization * Subjects must be off steroids without symptoms of CNS disease for at least 2 weeks prior to treatment * Subjects with signs or symptoms of brain metastasis are not eligible unless brain metastasis is ruled out by computed tomography or magnetic resonance imaging * Patients with uveal or mucosal melanoma are excluded * Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders such as vitiligo, alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll * Subjects with history of chronic liver disease, veno-occlusive disease, active alcohol abuse or illicit drug use other than marijuana or its derivatives * Uncontrolled or significant cardiovascular disease including but not limited to the following: * Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent * Uncontrolled angina within the 3 months prior to consent * Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation) * History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc) * Cardiovascular disease-related requirement for daily supplemental oxygen * Subjects with history of myocarditis, regardless of etiology * Baseline left ventricular ejection fraction (LVEF) \<45%. ECHO/MUGA not required at screening unless history of significant cardiac history. * QTc prolongation \> 500 msec * Uncontrolled or significant pulmonary disease including but not limited to the following: * Obstructive or restrictive lung disease requiring home oxygen * Hospitalization with chronic obstructive pulmonary disease (COPD) exacerbation within the last 6 months * History or concurrent condition of interstitial lung disease of any severity * Prior history of pneumonitis of grade II or higher, regardless of cause * Patients with diagnosis of obstructive sleep apnea (OSA) who are compliant with prescribed therapy (nocturnal O2, CPAP or BiPAP) are allowed on study * Uncontrolled or significant infectious disease including but not limited to the following: * Ongoing treatment for systemic bacterial, fungal or viral infection at screening * Subjects are not excluded for antimicrobial, antifungal or antiviral prophylaxis if other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | Up to 29 months | Best Response per RECIST v1.1: Completed Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis); Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum diameters while on study. Progressive Disease (PD): ≥20% (relative) increase in sum of diameters of target lesions referencing smallest sum on study (includes baseline sum if is smallest on study) and, the sum must also demonstrate an absolute increase of at least 5 mm; appearance of one or more new lesions. |
| Change in CD 8+ TIL Frequency | Baseline to Week 4 | CyTek flow cytometry will be used to evaluate tumor-infiltrating cells in PBMCs and tumor tissue for the increased frequency (proliferation) and activation of CD8+ TILs. Proliferation of CD8+ TIL cells correlate with improved survival in patients with melanoma. |
| Best Overall Response Rate (ORR) | Up to 29 months | Proportion of patients with a Best Response (CR+PR)/(CR+PR+SD+PD) per RECIST v1.1 of Completed Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis); or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| DLTs by Phase I Dose of Duvelisib With Nivolumab | Up to 56 days (per patient) | Number of patients experiencing acute dose limiting toxicities (DLTs) and laboratory abnormalities considered possibly related to study treatment, occurring from the initial dose of duvelisib + nivolumab through day 28 of treatment (acute) or toxicities occurring from day 29 through 28 days after completion of treatment (late toxicities). DLTs are defined using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Late Adverse Events at Least Possibly Related to Treatment | Beginning at 4 weeks after start of treatment, up to 14 months | Number and percentage of Late occurring adverse events as graded by CTCAE v5.0 in patients at each dosing interval and in the expansion cohort. Toxicity events include those that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0). |
| Treatment Related Adverse Events | Up to 42.5 months | Number of patients who experienced adverse events that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0). |
| Treatment Related Serious Adverse Events | Up to 42.5 months | Number of patients who experienced serious adverse events that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0). |
| Treatment-related Grade 3 or Higher AE | Up to 42.5 months | Number of Patients with Treatment-related Grade 3 or Higher AE per CTCAE v5.0 |
| Number of Patients With Clinical Response | Up to 36 months | Number of patients with Complete Response (CR) or Partial Response (PR) until the first time at which progressive disease is objectively documented per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumormarker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Overall Survival (OS) | Up to 25 months | The (median) length of time from the start of treatment that patients remain alive, until death from any cause. Patients who are alive will be censored at the time of the last follow-up. |
| 6-month Overall Survival (OS) | At 6 months | The percentage of patients alive at 6 months the start of treatment until death from any cause. |
| 12-month Overall Survival (OS) | At 12 months | The percentage of patients alive at 12 months the start of treatment until death from any cause. |
| 18-month Overall Survival (OS) | At 18 months | The percentage of patients alive at 18 months the start of treatment until death from any cause. |
| 6-month Overall Survival (OS) - Total Population | At 6 months | The percentage of patients alive at 6 months the start of treatment until death from any cause. |
| 12-month Overall Survival (OS) - Total Population | At 12 months | The percentage of patients alive at 12 months the start of treatment until death from any cause. |
| 18-month Overall Survival (OS) -Total Population | At 18 months | The percentage of patients alive at 18 months the start of treatment until death from any cause. |
| Progression-free Survival (PFS) | Up to 36 months | The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. |
| 6-month Progression-free Survival (PFS) | At 6 months | The percentage of patients whose disease does not progress from initial date of treatment to at 6 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. |
| 12-month Progression-free Survival (PFS) | At 12 months | The percentage of patients whose disease does not progress from initial date of treatment to at 12 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. |
| 18-month Progression-free Survival (PFS) | At 18 months | The percentage of patients whose disease does not progress from initial date of treatment to at 18 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. |
| Progression-free Survival (PFS) - Total Population | Up to 36 months | The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. |
| 6-month Progression-free Survival (PFS) - Total Population | At 6 months | The percentage of patients whose disease does not progress from initial date of treatment to at 6 months, with progression defined by RECIST v1.1. Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. |
| 12-month Progression-free Survival (PFS) - Total Population | At 12 months | The percentage of patients whose disease does not progress from initial date of treatment to at 12 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. |
| 18-month Progression-free Survival (PFS) - Total Population | At 18 months | The percentage of patients whose disease does not progress from initial date of treatment to at 18 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. |
| Overall Survival (OS) - Total Population | Up to 25 months | The (median) length of time from the start of treatment that patients remain alive, until death from any cause. Patients who are alive will be censored at the time of the last follow-up. |
| Clinical Benefit | At Week 12 | Complete response \[CR\], partial response \[PR\] or stable disease \[SD\], per RECIST v1.1 criteria . Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): ≥20% (relative) increase in sum of diameters of target lesions referencing smallest sum on study (includes baseline sum if is smallest on study) and, the sum must also demonstrate an absolute increase of at least 5 mm; appearance of one or more new lesions. |
| Clinical Benefit Rate | At Week 12 | Proportion of patients (CR + PR + SD)/(CR + PR + SD +PD) Complete response \[CR\], partial response \[PR\], stable disease \[SD\], per RECIST v1.1 criteria. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): ≥20% (relative) increase in sum of diameters of target lesions referencing smallest sum on study (includes baseline sum if is smallest on study) and, the sum must also demonstrate an absolute increase of at le |
| Acute Adverse Events at Least Possibly Related to Treatment | Up to 4 weeks | Number and percentage of Acute adverse events as graded by CTCAE v5.0 in patients at each dosing interval and in the expansion cohort. Toxicity events include those that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immune Cell Function | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) | Evaluation of peripheral blood mononuclear cells (PBMCs) using CyTek flow cytometry. |
| Mechanism of Anti-PD1 Resistance | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) | Changes in gene expression in the tumor using Nanostring gene profiling. |
| Tumor Microenvironment (TME) | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) | Changes in the immune cell population using Vectra imaging. |
Countries
United States
Participant flow
Pre-assignment details
No participants were enrolled in Phase 1: 25 mg BID Duvelisib and Phase II arms.
Participants by arm
| Arm | Count |
|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) Phase 1:
Duvelisib,15mg once a day, 12 hours a part, to determine the recommended dose for the Phase II study when combined with nivolumab.
Nivolumab, 240mg, IV, every 2 weeks for the first four cycles; thereafter it may be switched to 480mg, IV, once every 4 weeks (if deemed appropriate by the study doctor)
Phase II: The Recommended Phase II dosage of duvelisib administered will not be determined until Phase I is completed.
Nivolumab, 480mg, IV, every 4 weeks, for up to 1 year.
Nivolumab: Nivolumab is a human IgG4 monoclonal antibody that blocks PD-1. It is a type of immunotherapy and works as a checkpoint inhibitor, blocking a signal that prevents activation of T cells from attacking the cancer.
Duvelisib: Duvelisib is a potent inhibitor of both γ and δ isoforms. Duvelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. | 7 |
| Duvelisib (25mg) + Nivolumab (240mg) Phase 1:
Duvelisib,25mg once a day, 12 hours a part, to determine the recommended dose for the Phase II study when combined with nivolumab.
Nivolumab, 240mg, IV, every 2 weeks for the first four cycles; thereafter it may be switched to 480mg, IV, once every 4 weeks (if deemed appropriate by the study doctor) | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | Duvelisib (25mg) + Nivolumab (240mg) | Duvelisib (15mg) + Nivolumab (240mg) | Total |
|---|---|---|---|
| Age, Continuous | 65.50 years | 66.00 years | 66.00 years |
| BRAF Status Mutant | 0 Participants | 2 Participants | 2 Participants |
| BRAF Status Wild Type (WT) | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 7 | 5 / 6 |
| other Total, other adverse events | 7 / 7 | 6 / 6 |
| serious Total, serious adverse events | 6 / 7 | 4 / 6 |
Outcome results
Primary
Best Overall Response
Best Response per RECIST v1.1: Completed Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis); Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum diameters while on study. Progressive Disease (PD): ≥20% (relative) increase in sum of diameters of target lesions referencing smallest sum on study (includes baseline sum if is smallest on study) and, the sum must also demonstrate an absolute increase of at least 5 mm; appearance of one or more new lesions.
Time frame: Up to 29 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Best Overall Response | Partial Response (PR) | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Best Overall Response | Stable Disease (SD) | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Best Overall Response | Progressive Disease (PD) | 3 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Best Overall Response | Partial Response (PR) | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Best Overall Response | Stable Disease (SD) | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Best Overall Response | Progressive Disease (PD) | 3 Participants |
Primary
Best Overall Response Rate (ORR)
Proportion of patients with a Best Response (CR+PR)/(CR+PR+SD+PD) per RECIST v1.1 of Completed Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis); or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 29 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Best Overall Response Rate (ORR) | 0.20 proportion of patients |
| Duvelisib (25mg) + Nivolumab (240mg) | Best Overall Response Rate (ORR) | 0.0 proportion of patients |
Primary
Change in CD 8+ TIL Frequency
CyTek flow cytometry will be used to evaluate tumor-infiltrating cells in PBMCs and tumor tissue for the increased frequency (proliferation) and activation of CD8+ TILs. Proliferation of CD8+ TIL cells correlate with improved survival in patients with melanoma.
Time frame: Week 4 to Week 12
Population: Treated patients who provided samples for CD 8+ TIL testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total Cycling CD8 (%Ki67+) | 12.52 percentage of cells | Standard Deviation 26.54 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TCM. %CD8 | -1.88 percentage of cells | Standard Deviation 3.02 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total CD8 T-cells (%CD45) | 4.11 percentage of cells | Standard Deviation 4.59 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEM %CD8 | 4.03 percentage of cells | Standard Deviation 5.85 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | NAV. %CD8 | 1.44 percentage of cells | Standard Deviation 2.19 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEMRA. %CD8 | -3.62 percentage of cells | Standard Deviation 6.62 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | NAV. %CD8 | -1.70 percentage of cells | Standard Deviation 5.51 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total CD8 T-cells (%CD45) | -2.69 percentage of cells | Standard Deviation 0.69 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total Cycling CD8 (%Ki67+) | 2.92 percentage of cells | Standard Deviation 8.39 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEMRA. %CD8 | 8.20 percentage of cells | Standard Deviation 5.37 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TCM. %CD8 | -13.26 percentage of cells | Standard Deviation 6.73 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEM %CD8 | 6.75 percentage of cells | Standard Deviation 6.86 |
Primary
Change in CD 8+ TIL Frequency
CyTek flow cytometry will be used to evaluate tumor-infiltrating cells in PBMCs and tumor tissue for the increased frequency (proliferation) and activation of CD8+ TILs. Proliferation of CD8+ TIL cells correlate with improved survival in patients with melanoma.
Time frame: Baseline to Week 4
Population: Treated patients who provided samples for CD 8+ TIL testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total CD8 T-cells (%CD45) | -0.87 percentage of cells | Standard Deviation 2.91 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total Cycling CD8 (%Ki67+) | 2.86 percentage of cells | Standard Deviation 1.94 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | NAV. %CD8 | -2.52 percentage of cells | Standard Deviation 6.07 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TCM. %CD8 | 0.84 percentage of cells | Standard Deviation 3.89 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEM %CD8 | 2.92 percentage of cells | Standard Deviation 4.6 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEMRA. %CD8 | -1.25 percentage of cells | Standard Deviation 1.94 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEM %CD8 | 1.46 percentage of cells | Standard Deviation 4.98 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total CD8 T-cells (%CD45) | 2.66 percentage of cells | Standard Deviation 3.65 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TCM. %CD8 | -0.22 percentage of cells | Standard Deviation 5.13 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total Cycling CD8 (%Ki67+) | 10.26 percentage of cells | Standard Deviation 23.11 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEMRA. %CD8 | -0.88 percentage of cells | Standard Deviation 7.09 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | NAV. %CD8 | -1.44 percentage of cells | Standard Deviation 6.61 |
Primary
Change in CD 8+ TIL Frequency
CyTek flow cytometry will be used to evaluate tumor-infiltrating cells in PBMCs and tumor tissue for the increased frequency (proliferation) and activation of CD8+ TILs. Proliferation of CD8+ TIL cells correlate with improved survival in patients with melanoma.
Time frame: Baseline to Week 12
Population: Treated patients who provided samples for CD 8+ TIL testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total CD8 T-cells (%CD45) | 4.05 percentage of cells | Standard Deviation 5.03 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total Cycling CD8 (%Ki67+) | 15.86 percentage of cells | Standard Deviation 24.96 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | NAV. %CD8 | -3.79 percentage of cells | Standard Deviation 4.8 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TCM. %CD8 | -0.15 percentage of cells | Standard Deviation 3.23 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEM %CD8 | 7.97 percentage of cells | Standard Deviation 6.6 |
| Duvelisib (15mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEMRA. %CD8 | -4.06 percentage of cells | Standard Deviation 8.1 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEM %CD8 | 6.60 percentage of cells | Standard Deviation 6.65 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total CD8 T-cells (%CD45) | -1.63 percentage of cells | Standard Deviation 3.58 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TCM. %CD8 | -8.91 percentage of cells | Standard Deviation 3.41 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | Total Cycling CD8 (%Ki67+) | 0.45 percentage of cells | Standard Deviation 3.7 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | TEMRA. %CD8 | 4.00 percentage of cells | Standard Deviation 0.85 |
| Duvelisib (25mg) + Nivolumab (240mg) | Change in CD 8+ TIL Frequency | NAV. %CD8 | -1.68 percentage of cells | Standard Deviation 2.37 |
Primary
DLTs by Phase I Dose of Duvelisib With Nivolumab
Number of patients experiencing acute dose limiting toxicities (DLTs) and laboratory abnormalities considered possibly related to study treatment, occurring from the initial dose of duvelisib + nivolumab through day 28 of treatment (acute) or toxicities occurring from day 29 through 28 days after completion of treatment (late toxicities). DLTs are defined using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 56 days (per patient)
Population: Treated patients evaluated for dose limiting toxicities.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | DLTs by Phase I Dose of Duvelisib With Nivolumab | 0 participants |
| Duvelisib (25mg) + Nivolumab (240mg) | DLTs by Phase I Dose of Duvelisib With Nivolumab | 0 participants |
Secondary
12-month Overall Survival (OS)
The percentage of patients alive at 12 months the start of treatment until death from any cause.
Time frame: At 12 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 12-month Overall Survival (OS) | 80.0 percentage of patients |
| Duvelisib (25mg) + Nivolumab (240mg) | 12-month Overall Survival (OS) | 20.0 percentage of patients |
Secondary
12-month Overall Survival (OS) - Total Population
The percentage of patients alive at 12 months the start of treatment until death from any cause.
Time frame: At 12 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 12-month Overall Survival (OS) - Total Population | 50.0 percentage of patients |
Secondary
12-month Progression-free Survival (PFS)
The percentage of patients whose disease does not progress from initial date of treatment to at 12 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time frame: At 12 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 12-month Progression-free Survival (PFS) | 0 percentage of participants |
| Duvelisib (25mg) + Nivolumab (240mg) | 12-month Progression-free Survival (PFS) | 0 percentage of participants |
Secondary
12-month Progression-free Survival (PFS) - Total Population
The percentage of patients whose disease does not progress from initial date of treatment to at 12 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time frame: At 12 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 12-month Progression-free Survival (PFS) - Total Population | 0 percentage of patients |
Secondary
18-month Overall Survival (OS)
The percentage of patients alive at 18 months the start of treatment until death from any cause.
Time frame: At 18 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 18-month Overall Survival (OS) | 40.0 percentage of patients |
| Duvelisib (25mg) + Nivolumab (240mg) | 18-month Overall Survival (OS) | NA percentage of patients |
Secondary
18-month Overall Survival (OS) -Total Population
The percentage of patients alive at 18 months the start of treatment until death from any cause.
Time frame: At 18 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 18-month Overall Survival (OS) -Total Population | 30.0 percentage of patients |
Secondary
18-month Progression-free Survival (PFS)
The percentage of patients whose disease does not progress from initial date of treatment to at 18 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time frame: At 18 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 18-month Progression-free Survival (PFS) | 0 percentage of participants |
| Duvelisib (25mg) + Nivolumab (240mg) | 18-month Progression-free Survival (PFS) | 0 percentage of participants |
Secondary
18-month Progression-free Survival (PFS) - Total Population
The percentage of patients whose disease does not progress from initial date of treatment to at 18 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time frame: At 18 months
Population: Treated patients who were radiologically evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 18-month Progression-free Survival (PFS) - Total Population | 0 percentage of participants |
Secondary
6-month Overall Survival (OS)
The percentage of patients alive at 6 months the start of treatment until death from any cause.
Time frame: At 6 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 6-month Overall Survival (OS) | 80.0 percentage of patients |
| Duvelisib (25mg) + Nivolumab (240mg) | 6-month Overall Survival (OS) | 40.0 percentage of patients |
Secondary
6-month Overall Survival (OS) - Total Population
The percentage of patients alive at 6 months the start of treatment until death from any cause.
Time frame: At 6 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 6-month Overall Survival (OS) - Total Population | 60.0 percentage of patients |
Secondary
6-month Progression-free Survival (PFS)
The percentage of patients whose disease does not progress from initial date of treatment to at 6 months, with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time frame: At 6 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 6-month Progression-free Survival (PFS) | 20 percentage of participants |
| Duvelisib (25mg) + Nivolumab (240mg) | 6-month Progression-free Survival (PFS) | 0 percentage of participants |
Secondary
6-month Progression-free Survival (PFS) - Total Population
The percentage of patients whose disease does not progress from initial date of treatment to at 6 months, with progression defined by RECIST v1.1. Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time frame: At 6 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | 6-month Progression-free Survival (PFS) - Total Population | 10.0 percentage of patients |
Secondary
Acute Adverse Events at Least Possibly Related to Treatment
Number and percentage of Acute adverse events as graded by CTCAE v5.0 in patients at each dosing interval and in the expansion cohort. Toxicity events include those that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0).
Time frame: Up to 4 weeks
Population: All treated patients.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Anemia | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Vomiting | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Diarrhea | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Chills | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Fever | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | CD4 lymphocytes decreased | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Hyponatremia | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Myalgia | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Myalgia | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Fever | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Vomiting | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Anemia | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Hyponatremia | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Diarrhea | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | CD4 lymphocytes decreased | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Acute Adverse Events at Least Possibly Related to Treatment | Chills | 1 Participants |
Secondary
Clinical Benefit
Complete response \[CR\], partial response \[PR\], stable disease \[SD\], per RECIST v1.1 criteria . Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): ≥20% (relative) increase in sum of diameters of target lesions referencing smallest sum on study (includes baseline sum if is smallest on study) and, the sum must also demonstrate an absolute increase of at least 5 mm; appearance of one or more new lesions.
Time frame: At Week 48
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Clinical Benefit | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Clinical Benefit | 0 Participants |
Secondary
Clinical Benefit
Complete response \[CR\], partial response \[PR\] or stable disease \[SD\], per RECIST v1.1 criteria . Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): ≥20% (relative) increase in sum of diameters of target lesions referencing smallest sum on study (includes baseline sum if is smallest on study) and, the sum must also demonstrate an absolute increase of at least 5 mm; appearance of one or more new lesions.
Time frame: At Week 12
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Clinical Benefit | Partial Response (Week 12) | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Clinical Benefit | Stable Disease (Week 12) | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Clinical Benefit | Progressive Disease (Week 12) | 4 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Clinical Benefit | Partial Response (Week 12) | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Clinical Benefit | Stable Disease (Week 12) | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Clinical Benefit | Progressive Disease (Week 12) | 3 Participants |
Secondary
Clinical Benefit
Complete response \[CR\], partial response \[PR\], stable disease \[SD\], per RECIST v1.1 criteria . Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): ≥20% (relative) increase in sum of diameters of target lesions referencing smallest sum on study (includes baseline sum if is smallest on study) and, the sum must also demonstrate an absolute increase of at least 5 mm; appearance of one or more new lesions.
Time frame: At Week 24
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Clinical Benefit | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Clinical Benefit | 0 Participants |
Secondary
Clinical Benefit Rate
Proportion of patients (CR + PR + SD)/(CR + PR + SD +PD) Complete response \[CR\], partial response \[PR\], stable disease \[SD\], per RECIST v1.1 criteria. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): ≥20% (relative) increase in sum of diameters of target lesions referencing smallest sum on study (includes baseline sum if is smallest on study) and, the sum must also demonstrate an absolute increase of at le
Time frame: At Week 12
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Clinical Benefit Rate | 0.20 proportion of patients |
| Duvelisib (25mg) + Nivolumab (240mg) | Clinical Benefit Rate | 0.25 proportion of patients |
Secondary
Late Adverse Events at Least Possibly Related to Treatment
Number and percentage of Late occurring adverse events as graded by CTCAE v5.0 in patients at each dosing interval and in the expansion cohort. Toxicity events include those that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0).
Time frame: Beginning at 4 weeks after start of treatment, up to 14 months
Population: All treated patients.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Fatigue | 2 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Diarrhea | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Hepatic failure | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Aspartate aminotransferase increased | 3 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Alanine aminotransferase increased | 3 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Vomiting | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Blood bilirubin increased | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Generalized muscle weakness | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Lymphocyte count decreased | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Hypothyroidism | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Neutrophil count decreased | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Alkaline phosphatase increased | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | White blood cell decreased | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Dry mouth | 0 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Anorexia | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Proteinuria | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | CD4 lymphocytes decreased | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Hypertension | 1 Participants |
| Duvelisib (15mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Hyperthyroidism | 2 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Hypertension | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Alanine aminotransferase increased | 3 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Alkaline phosphatase increased | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Generalized muscle weakness | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Diarrhea | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Vomiting | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Hypothyroidism | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Dry mouth | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | CD4 lymphocytes decreased | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Fatigue | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Hepatic failure | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Aspartate aminotransferase increased | 3 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Blood bilirubin increased | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Lymphocyte count decreased | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Neutrophil count decreased | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | White blood cell decreased | 1 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Anorexia | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Proteinuria | 0 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Late Adverse Events at Least Possibly Related to Treatment | Hyperthyroidism | 0 Participants |
Secondary
Number of Patients With Clinical Response
Number of patients with Complete Response (CR) or Partial Response (PR) until the first time at which progressive disease is objectively documented per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumormarker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 36 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Number of Patients With Clinical Response | 1 participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Number of Patients With Clinical Response | 0 participants |
Secondary
Overall Survival (OS)
The (median) length of time from the start of treatment that patients remain alive, until death from any cause. Patients who are alive will be censored at the time of the last follow-up.
Time frame: Up to 25 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.~Among the 13 enrolled patients, 3 (2 in the 15 mg arm and 1 in the 25mg arm) were not evaluable as, per protocol, no duvelisib pills were returned for these patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Overall Survival (OS) | 13.5 months |
| Duvelisib (25mg) + Nivolumab (240mg) | Overall Survival (OS) | 4.9 months |
Secondary
Overall Survival (OS) - Total Population
The (median) length of time from the start of treatment that patients remain alive, until death from any cause. Patients who are alive will be censored at the time of the last follow-up.
Time frame: Up to 25 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Overall Survival (OS) - Total Population | 9.9 months |
Secondary
Progression-free Survival (PFS)
The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time frame: Up to 36 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Progression-free Survival (PFS) | 2.8 months |
| Duvelisib (25mg) + Nivolumab (240mg) | Progression-free Survival (PFS) | 3.0 months |
Secondary
Progression-free Survival (PFS) - Total Population
The (median) length of time from the initial date of treatment to the date of documented progression, or the date of death due to any cause (in the absence of progression, whichever occurs first), with progression defined by RECIST v1.1. PerRECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.
Time frame: Up to 36 months
Population: Patients who received at least one cycle of the treatment and at least one efficacy evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Progression-free Survival (PFS) - Total Population | 2.8 months |
Secondary
Treatment Related Adverse Events
Number of patients who experienced adverse events that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0).
Time frame: Up to 42.5 months
Population: All treated patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Treatment Related Adverse Events | 5 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Treatment Related Adverse Events | 5 Participants |
Secondary
Treatment-related Grade 3 or Higher AE
Number of Patients with Treatment-related Grade 3 or Higher AE per CTCAE v5.0
Time frame: Up to 42.5 months
Population: All treated patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Treatment-related Grade 3 or Higher AE | 4 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Treatment-related Grade 3 or Higher AE | 4 Participants |
Secondary
Treatment Related Serious Adverse Events
Number of patients who experienced serious adverse events that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0).
Time frame: Up to 42.5 months
Population: All treated patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib (15mg) + Nivolumab (240mg) | Treatment Related Serious Adverse Events | 3 Participants |
| Duvelisib (25mg) + Nivolumab (240mg) | Treatment Related Serious Adverse Events | 1 Participants |
Other Pre-specified
Immune Cell Function
Evaluation of peripheral blood mononuclear cells (PBMCs) using CyTek flow cytometry.
Time frame: Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort)
Other Pre-specified
Immune Cell Function
Evaluation of tumor-infiltrating cells from using CyTek flow cytometry.
Time frame: Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort)
Other Pre-specified
Mechanism of Anti-PD1 Resistance
Changes in gene expression in the tumor using Nanostring gene profiling.
Time frame: Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort)
Other Pre-specified
Tumor Microenvironment (TME)
Changes in the immune cell population using Vectra imaging.
Time frame: Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort)