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Unresectable MelanomaPhase 1/2NCT04688658

Duvelisib in Combination With Nivolumab in Patients With Advanced Unresectable Melanoma

A Phase 1/2 study testing Nivolumab and Duvelisib in people with Unresectable Melanoma, run by John Kirkwood at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Unresectable Melanoma
What is being tested?
Nivolumab and Duvelisib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
6 Oct 2021to 1 Feb 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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/exclusion criteria are met
  • Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection (i.e., subjects with known history of detectable viral load)
  • Infection with hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or human T-lymphotropic virus type 1
  • Subjects with a positive hepatitis B surface antigen [HBsAg] or hepatitis C antibody [HCV Ab] will be excluded, unless documented treatment and resolution of hepatitis C treatment Subjects with a positive hepatitis B core antibody (HBcAb) must have negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) assay to be eligible, must receive prophylaxis with entecavir (or equivalent) concomitant with duvelisib treatment, and must be periodically monitored for HBV reactivation by institutional guidelines. If unable to receive prophylaxis, then case will be discussed with investigators to determine eligibility.
  • History of tuberculosis treatment within 2 years prior to enrollment
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: A Phase I/II Study of PI3Kγδ Inhibitor Duvelisib in Combination With Nivolumab in Patients With Advanced Unresectable Melanoma Who Have Progressed on Anti-PD1 Therapy

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.

Read the 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.

Being tested
Nivolumab, Duvelisib
Keywords
Anti-PD-1 monoclonal antibody (mAb)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo, AG013736

    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.

  • DuvelisibDrug

    Also called Copiktra

    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.

Study groups in NCT04688658
Study groupRoleWhat they receive
Duvelisib plus NivolumabExperimentalPhase 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.
Receives: Drug: Nivolumab; Drug: Duvelisib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 56 days (per patient)

  2. 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.

    Measured: Up to 29 months

  3. 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.

    Measured: Up to 29 months

  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.

    Measured: Baseline to Week 4

  5. 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.

    Measured: Baseline to Week 12

  6. 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.

    Measured: Week 4 to Week 12

Secondary outcomes (26)

  1. 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.

    Measured: At Week 12

  2. 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.

    Measured: At Week 24

  3. 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.

    Measured: At Week 48

  4. 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

    Measured: At Week 12

  5. 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).

    Measured: Up to 4 weeks

  6. 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).

    Measured: Beginning at 4 weeks after start of treatment, up to 14 months

  7. 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).

    Measured: Up to 42.5 months

  8. 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).

    Measured: Up to 42.5 months

  9. Treatment-related Grade 3 or Higher AE

    Number of Patients with Treatment-related Grade 3 or Higher AE per CTCAE v5.0

    Measured: Up to 42.5 months

  10. 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.

    Measured: Up to 36 months

  11. 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.

    Measured: Up to 25 months

  12. 6-month Overall Survival (OS)

    The percentage of patients alive at 6 months the start of treatment until death from any cause.

    Measured: At 6 months

  13. 12-month Overall Survival (OS)

    The percentage of patients alive at 12 months the start of treatment until death from any cause.

    Measured: At 12 months

  14. 18-month Overall Survival (OS)

    The percentage of patients alive at 18 months the start of treatment until death from any cause.

    Measured: At 18 months

  15. 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.

    Measured: Up to 25 months

  16. 6-month Overall Survival (OS) - Total Population

    The percentage of patients alive at 6 months the start of treatment until death from any cause.

    Measured: At 6 months

  17. 12-month Overall Survival (OS) - Total Population

    The percentage of patients alive at 12 months the start of treatment until death from any cause.

    Measured: At 12 months

  18. 18-month Overall Survival (OS) -Total Population

    The percentage of patients alive at 18 months the start of treatment until death from any cause.

    Measured: At 18 months

  19. 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.

    Measured: Up to 36 months

  20. 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.

    Measured: At 6 months

  21. 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.

    Measured: At 12 months

  22. 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.

    Measured: At 18 months

  23. 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.

    Measured: Up to 36 months

  24. 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.

    Measured: At 6 months

  25. 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.

    Measured: At 12 months

  26. 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.

    Measured: At 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Dec 2020
  2. Study start6 Oct 2021
  3. Primary completion22 Feb 2024
  4. Study completion1 Feb 2025

Why it stopped: Secura Bio, Inc. discontinued support of the trial.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04688658
Sponsor's protocol ID
HCC 20-155
Status last verified
Aug 2025
First submitted
23 Dec 2020
Last updated
17 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab and Duvelisib in people with Unresectable Melanoma, run by John Kirkwood at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 48 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DLTs by Phase I Dose of Duvelisib With Nivolumab (time frame: Up to 56 days (per patient)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04688658.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.

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