Not provided
Not provided
Not provided
Not provided
Not provided
Secura Bio, Inc. discontinued support of the trial.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Secura Bio, Inc. | INDUSTRY |
| Bristol-Myers Squibb | INDUSTRY |
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Duvelisib plus Nivolumab | Experimental | Phase 1: Duvelisib will be taken orally in doses from 15mg once a day, 25mg once a day or 25mg twice 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nivolumab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 56 days (per patient) |
| 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. | Up to 29 months |
| 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. | Up to 29 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Immune Cell Function | Evaluation of peripheral blood mononuclear cells (PBMCs) using CyTek flow cytometry. | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) |
| Immune Cell Function |
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:
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:
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:
Uncontrolled or significant pulmonary disease including but not limited to the following:
Uncontrolled or significant infectious disease including but not limited to the following:
Patients with history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
Ongoing chronic treatment with immunosuppressants (e.g. cyclosporine) or systemic steroids > 10mg of prednisone or equivalent once daily. Topical and inhaled steroids are allowed.
Subjects with other uncontrolled medical conditions or other illnesses, laboratory findings or other factors that would, in the investigator's judgment, increase the risk to the subject associated with his or her participation in the study.
Patients who are receiving other investigational therapies will be excluded
Patients who had a history of life-threatening toxicity related to prior immune therapy (e.g. anti-CTLA-4, anti-PD1 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are well controlled an unlikely to be an issue with standard countermeasures (e.g. endocrine disorders managed by hormone replacement).
Subjects with a history of grade II or greater immune-mediated colitis. Patients whose toxicity was clearly attributable to anti-CTLA-4 treatment (tolerated anti-PD1 after receiving anti-CTLA4) may still be allowed on trial.
Subjects with a history of grade II or greater pneumonitis or transaminitis.
Prior treatments with PI3K inhibitors
Subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone therapy with curative intent, or treated in situ cervical cancer for which there is appropriate ongoing surveillance
Subject had therapy with radiation, surgery or chemotherapy within 4 weeks prior to time of consent and/or has not recovered from adverse events to due to prior therapy. Subjects should be adequately recovered from all toxicities, complications, or acute illnesses prior to starting investigational therapy.
A maximum of three patients who have received talimogene laherparepvec (T-vec) as prior therapy will be allowed to enroll in the Phase II portion of the study. However, study-related biopsies must be performed at a disease site that was not injected with T-vec or adjacent to a T-vec injection site.
Subjects who are unable or unwilling to take prophylaxis for Pneumocystis jirovecii, human simplex virus (HSV) or herpes zoster (VZV) at time of screening
Subjects with known hypersensitivity to duvelisib and/or its excipients: Microcrystalline cellulose and magnesium stearate
Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
Subjects who are unable or unwilling to comply with restrictions and prohibited activities and treatments
Subjects who are unable or unwilling to undergo venipuncture or tolerate venous access
Subjects with prior surgery and/or chronic gastrointestinal dysfunction that may affect drug absorption, such as gastric bypass, gastrectomy, malabsorption, inflammatory bowel disease, chronic diarrhea
Concurrent administration of medications or foods that are strong inhibitors of inducers of cytochrome p450 3A (CYP3A) within 2 weeks prior to study intervention. Duvelisib can increase exposure to CYP3A4 substrates; consider dose reduction of such substrates and monitor for signs of toxicities of co-administered sensitive CYP3A substrates.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| John Kirkwood, MD | UPMC Hillman Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | 15232 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
No participants were enrolled in Phase 1: 25 mg BID Duvelisib and Phase II arms.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Treated patients evaluated for dose limiting toxicities. | Posted | Number | participants | Up to 56 days (per patient) |
|
Adverse events data collected for up to 42.5 months for the study population.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | CARDIAC DISORDERS | CTCAE (5.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | BLOOD AND LYMPHATIC SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Barbara Stadterman, MPH, CCRP | UPMC Hillman Cancer Center | 4126475554 | stadtermanbm@upmc.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 27, 2022 | Feb 20, 2025 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| D000077784 | Axitinib |
| C586691 | duvelisib |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Duvelisib | Drug | 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. |
|
|
| 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. |
| Baseline to Week 4 |
| 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. | Baseline to Week 12 |
| 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. | Week 4 to Week 12 |
| At Week 12 |
| 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. | At Week 24 |
| 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. | At Week 48 |
| 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 | At Week 12 |
| 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). | Up to 4 weeks |
| 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). | Beginning at 4 weeks after start of treatment, up to 14 months |
| 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). | Up to 42.5 months |
| 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). | Up to 42.5 months |
| Treatment-related Grade 3 or Higher AE | Number of Patients with Treatment-related Grade 3 or Higher AE per CTCAE v5.0 | Up to 42.5 months |
| 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. | Up to 36 months |
| 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. | Up to 25 months |
| 6-month Overall Survival (OS) | The percentage of patients alive at 6 months the start of treatment until death from any cause. | At 6 months |
| 12-month Overall Survival (OS) | The percentage of patients alive at 12 months the start of treatment until death from any cause. | At 12 months |
| 18-month Overall Survival (OS) | The percentage of patients alive at 18 months the start of treatment until death from any cause. | At 18 months |
| 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. | Up to 25 months |
| 6-month Overall Survival (OS) - Total Population | The percentage of patients alive at 6 months the start of treatment until death from any cause. | At 6 months |
| 12-month Overall Survival (OS) - Total Population | The percentage of patients alive at 12 months the start of treatment until death from any cause. | At 12 months |
| 18-month Overall Survival (OS) -Total Population | The percentage of patients alive at 18 months the start of treatment until death from any cause. | At 18 months |
| 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. | Up to 36 months |
| 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. | At 6 months |
| 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. | At 12 months |
| 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. | At 18 months |
| 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. | Up to 36 months |
| 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. | At 6 months |
| 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. | At 12 months |
| 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. | At 18 months |
Evaluation of tumor-infiltrating cells from using CyTek flow cytometry.
| Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) |
| Tumor Microenvironment (TME) | Changes in the immune cell population using Vectra imaging. | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) |
| Mechanism of Anti-PD1 Resistance | Changes in gene expression in the tumor using Nanostring gene profiling. | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) |
| BG001 | 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) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| BRAF Status | BRAF mutations are found in roughly half of melanomas. Medications that target these mutations have improved survival rates of metastatic melanoma setting. | Count of Participants | Participants |
|
| OG001 | 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) |
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Count of Participants | Participants | Up to 29 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | proportion of patients | Up to 29 months |
|
|
|
| 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. | Treated patients who provided samples for CD 8+ TIL testing. | Posted | Mean | Standard Deviation | percentage of cells | Baseline to Week 4 |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Count of Participants | Participants | At Week 12 |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Count of Participants | Participants | At Week 24 |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Count of Participants | Participants | At Week 48 |
|
|
|
| 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 | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | proportion of patients | At Week 12 |
|
|
|
| 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). | All treated patients. | Posted | Count of Participants | Participants | Up to 4 weeks |
|
|
|
| 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). | All treated patients. | Posted | Count of Participants | Participants | Beginning at 4 weeks after start of treatment, up to 14 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). | All treated patients. | Posted | Count of Participants | Participants | Up to 42.5 months |
|
|
|
| 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). | All treated patients. | Posted | Count of Participants | Participants | Up to 42.5 months |
|
|
|
| Secondary | Treatment-related Grade 3 or Higher AE | Number of Patients with Treatment-related Grade 3 or Higher AE per CTCAE v5.0 | All treated patients. | Posted | Count of Participants | Participants | Up to 42.5 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | participants | Up to 36 months |
|
|
|
| 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. | 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. | Posted | Median | 95% Confidence Interval | months | Up to 25 months |
|
|
|
| Secondary | 6-month Overall Survival (OS) | The percentage of patients alive at 6 months the start of treatment until death from any cause. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of patients | At 6 months |
|
|
|
| Secondary | 12-month Overall Survival (OS) | The percentage of patients alive at 12 months the start of treatment until death from any cause. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of patients | At 12 months |
|
|
|
| Secondary | 18-month Overall Survival (OS) | The percentage of patients alive at 18 months the start of treatment until death from any cause. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of patients | At 18 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Median | 95% Confidence Interval | months | Up to 25 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of patients | At 6 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of patients | At 12 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of patients | At 18 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Median | 95% Confidence Interval | months | Up to 36 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of participants | At 6 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of participants | At 12 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of participants | At 18 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Median | 95% Confidence Interval | months | Up to 36 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of patients | At 6 months |
|
|
|
| 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. | Patients who received at least one cycle of the treatment and at least one efficacy evaluation. | Posted | Number | 95% Confidence Interval | percentage of patients | At 12 months |
|
|
|
| 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. | Treated patients who were radiologically evaluable. | Posted | Number | 95% Confidence Interval | percentage of participants | At 18 months |
|
|
|
| Other Pre-specified | Immune Cell Function | Evaluation of peripheral blood mononuclear cells (PBMCs) using CyTek flow cytometry. | Not Posted | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) | Participants |
| Other Pre-specified | Immune Cell Function | Evaluation of tumor-infiltrating cells from using CyTek flow cytometry. | Not Posted | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) | Participants |
| Other Pre-specified | Tumor Microenvironment (TME) | Changes in the immune cell population using Vectra imaging. | Not Posted | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) | Participants |
| Other Pre-specified | Mechanism of Anti-PD1 Resistance | Changes in gene expression in the tumor using Nanostring gene profiling. | Not Posted | Baseline (prior to treatment), at 12 weeks after start of treatment; Up to 2 years (cohort) | Participants |
| 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. | Treated patients who provided samples for CD 8+ TIL testing. | Posted | Mean | Standard Deviation | percentage of cells | Baseline to Week 12 |
|
|
|
| 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. | Treated patients who provided samples for CD 8+ TIL testing. | Posted | Mean | Standard Deviation | percentage of cells | Week 4 to Week 12 |
|
|
|
| 7 |
| 7 |
| 6 |
| 7 |
| 7 |
| 7 |
| EG001 | 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) | 5 | 6 | 4 | 6 | 6 | 6 |
| Diarrhea | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Retroperitoneal hemorrhage | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Vomiting | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Death NOS | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Hepatic failure | HEPATOBILIARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Covid | INFECTIONS AND INFESTATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Lung infection | INFECTIONS AND INFESTATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Sepsis | INFECTIONS AND INFESTATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) -Other, specifyBrain |Neoplasm | NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) | CTCAE (5.0) | Systematic Assessment |
|
| Edema cerebral | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Encephalopathy | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Lethargy | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Seizure | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Confusion | PSYCHIATRIC DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Acute kidney injury | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Respiratory failure | RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| sternectomy with reconstruction | SURGICAL AND MEDICAL PROCEDURES | CTCAE (5.0) | Systematic Assessment |
|
| Eosinophilia | BLOOD AND LYMPHATIC SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Leukocytosis | BLOOD AND LYMPHATIC SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Pericardial effusion | CARDIAC DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Sinus bradycardia | CARDIAC DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Sinus tachycardia | CARDIAC DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hyperthyroidism | ENDOCRINE DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Dry eye | EYE DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Abdominal pain | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Constipation | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Diarrhea | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Dry mouth | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Nausea | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Vomiting | GASTROINTESTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Chills | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Edema limbs | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Fatigue | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Fever | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Pain | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Fall | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| lymph node pain | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| restlessness | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Back Pain | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Upper respiratory infection | INFECTIONS AND INFESTATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Bruising | INJURY, POISONING AND PROCEDURAL COMPLICATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Pain - Surgical | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Tumor |Pain - |Chest | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Generalized edema | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Non-cardiac chest pain | GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | CTCAE (5.0) | Systematic Assessment |
|
| Pneumonia | INFECTIONS AND INFESTATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Sepsis | INFECTIONS AND INFESTATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Thrush | INFECTIONS AND INFESTATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Urinary tract infection | INFECTIONS AND INFESTATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Alkaline phosphatase increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Blood bilirubin increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Cardiac troponin I increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| CD4 lymphocytes decreased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Creatinine increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| INR increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Elevated CRP | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Partial thromboplastin time increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Prothrombin time increased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Lymphocyte count decreased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Neutrophil count decreased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Platelet count decreased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Weight gain | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| White blood cell decreased | INVESTIGATIONS | CTCAE (5.0) | Systematic Assessment |
|
| Anorexia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Dehydration | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypercalcemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hyperglycemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hyperkalemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypermagnesemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypernatremia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypertriglyceridemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypoalbuminemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypocalcemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypoglycemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypokalemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypomagnesemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hyponatremia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypophosphatemia | METABOLISM AND NUTRITION DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Back pain | MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Generalized muscle weakness | MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Myalgia | MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Dysphasia | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Lethargy | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Somnolence | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Agitation | PSYCHIATRIC DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Dizziness | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Dysgeusia | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Headache | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Agitation | NERVOUS SYSTEM DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Anxiety | PSYCHIATRIC DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Confusion | PSYCHIATRIC DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Delirium | PSYCHIATRIC DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Acute kidney injury | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Chronic kidney disease | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hematuria | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Proteinuria | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Glucosuria | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hematuria | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Proteinuria | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Urine discoloration | RENAL AND URINARY DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Reproductive system and breast disorders - |Other, specifyLabial |Lesion |Pain | REPRODUCTIVE SYSTEM AND BREAST DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Reproductive system and breast disorders - |Other, specifypain (labia) | REPRODUCTIVE SYSTEM AND BREAST DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Cough | RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Epistaxis | RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Dyspnea | RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - |Other, specifyHemoptysis | RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Rash maculo-papular | SKIN AND SUBCUTANEOUS TISSUE DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Surgical and medical procedures - |Other, specifyCraniotomy | SURGICAL AND MEDICAL PROCEDURES | CTCAE (5.0) | Systematic Assessment |
|
| Rash acneiform | SKIN AND SUBCUTANEOUS TISSUE DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| deep tissue pressure injury on buttocks | SKIN AND SUBCUTANEOUS TISSUE DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hematoma | VASCULAR DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypertension | VASCULAR DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
| Hypotension | VASCULAR DISORDERS | CTCAE (5.0) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D007191 | Indazoles |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Progressive Disease (PD) |
|
| NAV. %CD8 |
|
| TCM. %CD8 |
|
| TEM %CD8 |
|
| TEMRA. %CD8 |
|
| Progressive Disease (Week 12) |
|
| Vomiting |
|
| Chills |
|
| Fever |
|
| CD4 lymphocytes decreased |
|
| Hyponatremia |
|
| Myalgia |
|
| Vomiting |
|
| Hypothyroidism |
|
| Dry mouth |
|
| CD4 lymphocytes decreased |
|
| Fatigue |
|
| Hepatic failure |
|
| Alanine aminotransferase increased |
|
| Alkaline phosphatase increased |
|
| Aspartate aminotransferase increased |
|
| Blood bilirubin increased |
|
| Lymphocyte count decreased |
|
| Neutrophil count decreased |
|
| White blood cell decreased |
|
| Anorexia |
|
| Generalized muscle weakness |
|
| Proteinuria |
|
| Hypertension |
|
| NAV. %CD8 |
|
| TCM. %CD8 |
|
| TEM %CD8 |
|
| TEMRA. %CD8 |
|
| NAV. %CD8 |
|
| TCM. %CD8 |
|
| TEM %CD8 |
|
| TEMRA. %CD8 |
|