Renal Cell CarcinomaPhase 1/2NCT04074967

Study of ARRY-614 Plus Either Nivolumab or Nivolumab+Ipilimumab

A Phase 1/2 study testing Phase Ib ARRY-614 + nivolumab, Phase Ib ARRY-614 + nivolumab+ipilimumab and Phase II ARRY-614 + nivolumab in people with Renal Cell Carcinoma and Melanoma, run by Dan Zandberg at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Renal Cell Carcinoma, Melanoma, Solid Tumor
What is being tested?: Phase Ib ARRY-614 + nivolumab, Phase Ib ARRY-614 + nivolumab+ipilimumab and Phase II ARRY-614 + nivolumab
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 70 participants
Where: 1 siteUnited States
Study dates: 11 Jun 2020to 31 Dec 2025
Phase: Phase 1/2
Are there results?: Not yet: the study is under way

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

Age ≥18 years.
For Phase Ib: Trial participants must have a histologically confirmed malignancy that is metastatic or unresectable for which curative measures do not exist or are no longer effective.
a.Trial participants must have nivolumab or ipilimumab therapy available and must be appropriate for this therapy.
For Phase II:
Participants with melanoma who previously experienced disease progression on anti-PD1 (with or without ipilimumab).
Participants with RCC who previously experienced disease progression on anti-PD1 (with or without ipilimumab).

Show all 27Show fewer

Participants with NSCLC or HNSCC who previously experienced disease progression on anti-PD1 (with or without ipilimumab).
Progression on prior anti-PD1/L1 or anti-PD1/anti-CTLA4 antibodies must meet definitions for primary or secondary resistance and regrowth after stopping therapy as below or there must be documentation by the treating investigator of rapid disease progression such that these criteria cannot be assessed (suggestions from the Society for ImmunoTherapy of Cancer PD1 Resistance Working Group).
Have an ECOG PS score of 0 or 1 (Appendix 13.A).
Have an expected survival of ≥3 months.
Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
The first five patients in each Phase II cohort must have tumors determined to be easily accessible for biopsy and must be willing to have two biopsies
Have recovered from toxicities associated with prior anticancer therapy to baseline or Grade 1 unless stabilized under medical management per investigator.
Have adequate bone marrow function as evidenced by:
Absolute neutrophil count ≥1,500/mm3 or 1.5 ×109/L
Hemoglobin ≥8 g/dL
Platelets ≥100,000/mm3 or 100 × 109/L
Have adequate hepatic function as evidenced by:
Serum total bilirubin ≤2 × upper limit of normal (ULN), unless considered due to Gilbert's disease
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x the institutional ULN or ≤ 5.0x institutional ULN in the presence of known liver metastases.
Patients with creatinine clearance > 30 mL/min, (measured using Cockcroft-Gault equation or the estimated glomerular filtration rate from the Modification of Diet in Renal Disease Study) are included in the study.
Be able to understand and willing to sign the informed consent form (or have legal representation) and to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including serial peripheral blood sampling, biopsies, and urine sampling, during the study. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent if acceptable to and approved by the site's IRB/Independent Ethics Committee (IEC).
Female patients with reproductive potential must have a negative serum pregnancy test prior to the start of therapy, or a confirmation from an obstetrician in case of equivocal serum pregnancy results. Females of reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion or who have not been naturally postmenopausal (ie, who have not menstruated) for at least 24 consecutive months (ie, have not had menses at any time in the preceding 24 consecutive months). Women with reproductive potential, as well as fertile men and their partners who are female with reproductive potential, must agree to use two effective forms of contraception (including at least one barrier form) from the time of giving informed consent throughout the study and for 5 months after the last dose of therapy for women, and 7 months after last dose for men. Effective forms of contraception are defined as hormonal PO contraceptives, injectables, patches, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal ligation, condoms with spermicide, or male partner sterilization.
Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have:
A stable regimen of highly active anti-retroviral therapy (HAART)
No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based test

Who cannot join

Received systemic anticancer therapy or an investigational agent <2 weeks prior to Day 1 (washout from prior immune based anticancer therapy is 4 weeks). In addition, the first dose of study treatment should not occur before a period ≥5 half-lives of the investigational agent has elapsed (excluding nivolumab therapy or combination anti-PD1/ipilimumab combination therapy in RCC - prior ipilimumab not permitted in melanoma cohort).
For ST, have underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks prior to Day 1.
Participants must not have had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (with exception of anti-PD1/ipilimumab combination therapy) or have not recovered (i.e. < Grade 1 at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Participants must not have a diagnosis of immunodeficiency or be receiving systemic steroid therapy at a dose of >10 mg prednisone daily or equivalent at time of first dose of trial treatment (this criterion does not apply to HIV-positive patients as detailed in the inclusion criteria).
Participants must not have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Participants must not have a known history of non-infectious pneumonitis that required steroids for treatment.

Show all 19Show fewer

Participants must not have evidence of active interstitial lung disease.
Have known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 1 week and have radiographically stable disease for at least 1 month prior to study entry. Note: up to 10 mg per day of prednisone equivalent will be allowed.
Have a history of another primary cancer that is active requiring treatment, progressing or for which the investigator believes will make disease assessment unreliable.
Underwent major surgery within 4 weeks of Day 1 or have not recovered from post-surgery toxicities.
Are pregnant or breastfeeding.
Have an active infection requiring systemic anti-infective therapy or with an unexplained fever >38.5°C within 7 days of Day 1 (at the discretion of the Investigator, patients with tumor fever may be enrolled).
Have any known hypersensitivity to any of the components of ARRY-614 or anti-PD1/ipilimumab combination therapies.
Have significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure); myocardial infarction; unstable angina; and/or stroke.
Have known LVEF <40% by ECHO scan (or by other methods according to institutional practice) obtained within 28 days prior to the start of study treatment (testing is not otherwise mandatory).
Have known active hepatitis B (HBV) or hepatitis C (HCV) infections. Patients with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted. Patients with chronic HBV that is adequately suppressed per institutional practice will be permitted.
Have any other acute or chronic medical or psychiatric condition, including recent (within 12 months of Day 1) or active suicidal ideation or behavior, or a laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
Have known active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered PO. Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential).
Have been committed to an institution by an order issued either by the judicial or administrative authorities.

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 Ib/II Study of ARRY-614 Plus Either Nivolumab or Nivolumab+Ipilimumab in Advanced Solid Tumors

In this study, the Phase Ib portion aims to establish safety and tolerability of ARRY-614 with either nivolumab or ipilimumab and to determine a recommended phase II dose of ARRY-614 in combination with either nivolumab or nivolumab+ipilimumab immunotherapy in patients with selected advanced solid tumors. The Phase II portion will estimate the efficacy of ARRY-614 in combination with either nivolumab or ARRY-614 + nivolumab+ipilimumab immunotherapy in patients with with NSCLC, HNSCC, melanoma and RCC and melanoma.

Read the detailed description

This phase Ib/II study of PO administered ARRY-614 in combination with checkpoint immunotherapy. In phase Ib, this includes ARRY-614 plus nivolumab or ARRY-614 + nivolumab+ipilimumab in patients with selected advanced solid tumors. In phase II, this includes ARRY-614 in combination with nivolumab in a combined cohort of NSCLC and HNSCCC as well as two arms with patients having either melanoma and RCC, where ARRY-614 will be combined with nivolumab+ipilimumab. The objective of the Ib phase is to determine the safety, tolerability and recommended phase II dose of ARRY-614 with either nivolumab or nivolumab+ipilimumab combination therapy. The objective of Phase II is to determine best ORR in the three separate phase II arms: ARRY-614 plus nivolumab+ipilimumab in melanoma or RCC as well as ARRY-614 plus nivolumab in a combined cohort of NSCLC and HNSCC. The recommended phase II dose will be informed by the phase Ib safety study of ARRY-614, the plasma PK of ARRY-614 and the metabolite, AR00451575, and the PD effects of ARRY-614 in pre and post dose peripheral blood samples.

In phase Ib, trial participants will take ARRY-614 continuously in 3- or 4-week cycles (± 3 days). Nivolumab and nivolumab+ipilimumab therapy will be dosed according to FDA-approved or compendium supported dosing schedule.

In phase II, a similar dosing schedule will be pursued once the recommended phase II dose of ARRY-614 has been determined with nivolumab or nivolumab +ipilimumab. ARRY-614 will be given on a daily PO schedule in 3- or 4-week cycles (± 3 days).

Conditions: Renal Cell Carcinoma, Melanoma, Solid Tumor, Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma
Being tested: Phase Ib ARRY-614 + nivolumab, Phase Ib ARRY-614 + nivolumab+ipilimumab, Phase II ARRY-614 + nivolumab, Phase II ARRY-614 + nivolumab+ipilimumab (melanoma), Phase II ARRY-614 + nivolumab+ipilimumab (RCC)
Medical subject headings: Carcinoma, Renal Cell, Melanoma, Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck

What participants receive

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

Phase Ib ARRY-614 + nivolumabDrug
ARRY-614 continuously in 4-week cycles (± 3 days). Nivolumab will be dosed according to FDA-approved dosing schedule.
Phase Ib ARRY-614 + nivolumab+ipilimumabDrug
ARRY-614 continuously in 4-week cycles (± 3 days). Nivolumab will be dosed according to FDA-approved dosing schedule. Ipilimumab therapy will be dosed according to FDA-approved dosing schedule.
Phase II ARRY-614 + nivolumabDrug
Recommended Phase II dose of ARRY-614 (to be determined) daily in 4-week cycles (± 3 days).
Nivolumab will be dosed according to FDA-approved dosing schedule.
Phase II ARRY-614 + nivolumab+ipilimumab (melanoma)Drug
Recommended Phase II dose of ARRY-614 (to be determined) daily in 4-week cycles (± 3 days).
Nivolumab will be dosed according to FDA-approved dosing schedule. Ipilimumab therapy will be dosed according to FDA-approved dosing schedule.
Phase II ARRY-614 + nivolumab+ipilimumab (RCC)Drug
Recommended Phase II dose of ARRY-614 (to be determined) daily in 4-week cycles (± 3 days).
Nivolumab will be dosed according to FDA-approved dosing schedule. Ipilimumab therapy will be dosed according to FDA-approved dosing schedule.

Study groups in NCT04074967
Study group	Role	What they receive
Phase Ib ARRY-614 + nivolumab	Experimental	Participants with advanced solid tumors will receive ARRY-614 in combination with nivolumab. (histologically confirmed metastatic or unresectable malignancy with lacking curative measures; nivolumab must be available and appropriate for proposed therapy) Receives: Drug: Phase Ib ARRY-614 + nivolumab
Phase Ib ARRY-614 + nivolumab + ipilimumab	Experimental	Participants with advanced solid tumors will received ARRY-614 in combination with nivolumab + ipilimumab. (histologically confirmed metastatic or unresectable malignancy with lacking curative measures; nivolumab and ipilimumab must be available and appropriate for proposed therapy) Receives: Drug: Phase Ib ARRY-614 + nivolumab+ipilimumab
Phase II ARRY-614 + nivolumab	Experimental	Participants with of NSCLC and HNSCCC will receive ARRY-614 combined with nivolumab. Receives: Drug: Phase II ARRY-614 + nivolumab
Phase II ARRY-614 + nivolumab + ipilimumab (melanoma)	Experimental	Participants with melanoma will receive ARRY-614 combined with nivolumab + ipilimumab. Receives: Drug: Phase II ARRY-614 + nivolumab+ipilimumab (melanoma)
Phase II ARRY-614 + nivolumab + ipilimumab (RCC)	Experimental	Participants with RCC will receive ARRY-614 combined with nivolumab + ipilimumab. Receives: Drug: Phase II ARRY-614 + nivolumab+ipilimumab (RCC)

What is being measured

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

Participants Experiencing a Dose Limiting Toxicity (DLT)
Safety and recommended Phase ll dose of ARRY-614 in combination with either nivolumab or or nivolumab+ipilimumab per NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.0: Any AE (unless attributable to an extraneous cause, ex. disease progression) that satisfies ≥1 of the following: Grade 3 or 4 nausea or vomiting; Grade 3 or 4 nausea or vomiting despite anti emetic prophylaxis; Grade 3 or 4 diarrhea; Grade 3 or 4 diarrhea despite the administration of anti-diarrheals. Other Grade 3 or 4 (except asymptomatic amylase/lipase or other asymptomatic biochemical marker that does not resolve with adequate treatment in ≤1 week). Hematologic AEs: Absolute neutrophil count (ANC) <500/mm^3 for ≥5 days, Febrile neutropenia (ANC < 1,000/mm^3 and single temperature ≥38.3 °C or sustained temperature of ≥38.0 °C for ≥1 hour), Platelets <25,000/mm^3, Hemoglobin <8.0 g/dL, Grade 3 hemorrhage associated with thrombocytopenia < Grade 4 (i.e. Grade 3 hemorrhage with platelets >25,000/mm^3).
Measured: Up to 28 days (during first cycle of treatment)
Objective Response
The probability of (objective) response to treatment (estimation). Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥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 PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥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). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 48 months

Secondary outcomes (5)

Adverse Events related to Study Treatment
The occurrence (number and type) of toxicity events in participants receiving ARRY-614 in combination with either nivolumab or or nivolumab+ipilimumab immunotherapy. Adverse Events and Serious Adverse Events per CTCAE v5.0 at least Possibly Related to Treatment at (Phase II dose).
Measured: Up to 48 months
Overall Survival (OS)
The length of time from the start of treatment that diagnosed participants remain alive, until the time of death from any cause.
Measured: Up to 48 months
Progression Free Survival (PRS)
The length of time from first dose of either drug until disease progression or death from any cause, whichever occurs first.Per RECIST v1.1: Progressive Disease (PD):≥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). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 48 months
Duration of Response
Time between the initial response to treatment per RECIST v1.1 and subsequent disease progression.
Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥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 PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥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). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 48 months
Response per Immune-related response criteria (irRECIST)
irCR (Complete Response):Disappearance of non-nodal lesions.All pathologic lymph nodes <10 mm (2 consecutive measures ≥4 weeks apart); irPR (Partial Response):≥30% decrease from baseline (2 consecutive measures ≥4 weeks apart); irPD (Progressive Disease):≥20% increase from nadir and ≥5mm (2 consecutive measures ≥4 weeks apart); irSD (Stable Disease): Not sufficient decrease for PR, nor sufficient increase for PD; irPR (Progressive Disease): Disappearance of all non-nodal lesions.All pathologic lymph nodes <10 mm (Non-Target Lesions:Any other than disappearance of all non-nodal lesions and reduction of pathologic lymph nodes <10 mm). Baseline tumor burden: sum of single diameters (short axis for nodal lesions, longest diameter for other lesions) for target lesions. In subsequent scans, the diameters of new measurable lesions are added to the tumor burden. Re-treatment: ≤5 target lesions (=/≠ original lesions) are selected and a new baseline tumor burden will be established.
Measured: Up to 48 months

Timeline

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

11 Jun 202031 Dec 2025

First posted30 Aug 2019
Study start11 Jun 2020
Primary completion27 Dec 2024
Study completion31 Dec 2025 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Non-randomised
Intervention model: Parallel groups
Model description: Phase lb: subjects with advanced solid tumors will receive ARRY-614 in combination with nivolumab or ARRY-614 in combination with nivolumab + ipilimumab immunotherapy. Phase ll: Subjects with NSCLC or HNSCC will receive ARRY-614 combined with nivolumab. Subjects with melanoma will receive ARRY-614 combined with nivolumab + ipilimumab. Subjects with RCC will receive ARRY-614 combined with nivolumab + ipilimumab.
Masking: None (open label)
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04074967
Sponsor's protocol ID: HCC 19-097
Status last verified: Nov 2025
First submitted: 19 Aug 2019
Last updated: 6 Nov 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma

All Renal Cell Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib/II Study of ARRY-614 Plus Either Nivolumab or Nivolumab+Ipilimumab in Advanced Solid Tumors
ClinicalTrials.gov ID: NCT04074967
Acronym / sponsor ID: HCC 19-097
Conditions: Renal Cell Carcinoma, Melanoma, Solid Tumor, Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 70 participants (actual)
Lead sponsor: Dan ZandbergUniversity, hospital or other
Collaborators: Array BioPharma
Study start: 11 Jun 2020 (actual)
Primary completion: 27 Dec 2024 (actual)
Study completion: 31 Dec 2025 (estimated)
First posted: 30 Aug 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5
Model description: Phase lb: subjects with advanced solid tumors will receive ARRY-614 in combination with nivolumab or ARRY-614 in combination with nivolumab + ipilimumab immunotherapy. Phase ll: Subjects with NSCLC or HNSCC will receive ARRY-614 combined with nivolumab. Subjects with melanoma will receive ARRY-614 combined with nivolumab + ipilimumab. Subjects with RCC will receive ARRY-614 combined with nivolumab + ipilimumab.

Arm	Type	Receives
Phase Ib ARRY-614 + nivolumab	Experimental	Drug: Phase Ib ARRY-614 + nivolumabParticipants with advanced solid tumors will receive ARRY-614 in combination with nivolumab. (histologically confirmed metastatic or unresectable malignancy with lacking curative measures; nivolumab must be available and appropriate for proposed therapy)
Phase Ib ARRY-614 + nivolumab + ipilimumab	Experimental	Drug: Phase Ib ARRY-614 + nivolumab+ipilimumabParticipants with advanced solid tumors will received ARRY-614 in combination with nivolumab + ipilimumab. (histologically confirmed metastatic or unresectable malignancy with lacking curative measures; nivolumab and ipilimumab must be available and appropriate for proposed therapy)
Phase II ARRY-614 + nivolumab	Experimental	Drug: Phase II ARRY-614 + nivolumabParticipants with of NSCLC and HNSCCC will receive ARRY-614 combined with nivolumab.
Phase II ARRY-614 + nivolumab + ipilimumab (melanoma)	Experimental	Drug: Phase II ARRY-614 + nivolumab+ipilimumab (melanoma)Participants with melanoma will receive ARRY-614 combined with nivolumab + ipilimumab.
Phase II ARRY-614 + nivolumab + ipilimumab (RCC)	Experimental	Drug: Phase II ARRY-614 + nivolumab+ipilimumab (RCC)Participants with RCC will receive ARRY-614 combined with nivolumab + ipilimumab.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (27 listed)

Age ≥18 years.
For Phase Ib: Trial participants must have a histologically confirmed malignancy that is metastatic or unresectable for which curative measures do not exist or are no longer effective.
a.Trial participants must have nivolumab or ipilimumab therapy available and must be appropriate for this therapy.
For Phase II:
Have an ECOG PS score of 0 or 1 (Appendix 13.A).

Key exclusion criteria (19 listed)

Received systemic anticancer therapy or an investigational agent <2 weeks prior to Day 1 (washout from prior immune based anticancer therapy is 4 weeks). In addition, the first dose of study treatment should not occur before a period ≥5 half-lives of the investigational agent has elapsed (excluding nivolumab therapy or combination anti-PD1/ipilimumab combination therapy in RCC - prior ipilimumab not permitted in melanoma cohort).
For ST, have underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks prior to Day 1.
Participants must not have had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (with exception of anti-PD1/ipilimumab combination therapy) or have not recovered (i.e. < Grade 1 at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Participants must not have a diagnosis of immunodeficiency or be receiving systemic steroid therapy at a dose of >10 mg prednisone daily or equivalent at time of first dose of trial treatment (this criterion does not apply to HIV-positive patients as detailed in the inclusion criteria).
Participants must not have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Phase Ib ARRY-614 + nivolumabARRY-614 continuously in 4-week cycles (± 3 days). Nivolumab will be dosed according to FDA-approved dosing schedule.	Drug	Phase Ib ARRY-614 + nivolumab
Phase Ib ARRY-614 + nivolumab+ipilimumabARRY-614 continuously in 4-week cycles (± 3 days). Nivolumab will be dosed according to FDA-approved dosing schedule. Ipilimumab therapy will be dosed according to FDA-approved dosing schedule.	Drug	Phase Ib ARRY-614 + nivolumab + ipilimumab
Phase II ARRY-614 + nivolumabRecommended Phase II dose of ARRY-614 (to be determined) daily in 4-week cycles (± 3 days). Nivolumab will be dosed according to FDA-approved dosing schedule.	Drug	Phase II ARRY-614 + nivolumab
Phase II ARRY-614 + nivolumab+ipilimumab (melanoma)Recommended Phase II dose of ARRY-614 (to be determined) daily in 4-week cycles (± 3 days). Nivolumab will be dosed according to FDA-approved dosing schedule. Ipilimumab therapy will be dosed according to FDA-approved dosing schedule.	Drug	Phase II ARRY-614 + nivolumab + ipilimumab (melanoma)
Phase II ARRY-614 + nivolumab+ipilimumab (RCC)Recommended Phase II dose of ARRY-614 (to be determined) daily in 4-week cycles (± 3 days). Nivolumab will be dosed according to FDA-approved dosing schedule. Ipilimumab therapy will be dosed according to FDA-approved dosing schedule.	Drug	Phase II ARRY-614 + nivolumab + ipilimumab (RCC)

Primary outcome

Participants Experiencing a Dose Limiting Toxicity (DLT)
Time frame: Up to 28 days (during first cycle of treatment)
Safety and recommended Phase ll dose of ARRY-614 in combination with either nivolumab or or nivolumab+ipilimumab per NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.0: Any AE (unless attributable to an extraneous cause, ex. disease progression) that satisfies ≥1 of the following: Grade 3 or 4 nausea or vomiting; Grade 3 or 4 nausea or vomiting despite anti emetic prophylaxis; Grade 3 or 4 diarrhea; Grade 3 or 4 diarrhea despite the administration of anti-diarrheals. Other Grade 3 or 4 (except asymptomatic amylase/lipase or other asymptomatic biochemical marker that does not resolve with adequate treatment in ≤1 week). Hematologic AEs: Absolute neutrophil count (ANC) <500/mm^3 for ≥5 days, Febrile neutropenia (ANC < 1,000/mm^3 and single temperature ≥38.3 °C or sustained temperature of ≥38.0 °C for ≥1 hour), Platelets <25,000/mm^3, Hemoglobin <8.0 g/dL, Grade 3 hemorrhage associated with thrombocytopenia < Grade 4 (i.e. Grade 3 hemorrhage with platelets >25,000/mm^3).
Objective Response
Time frame: Up to 48 months
The probability of (objective) response to treatment (estimation). Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥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 PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥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). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

5 secondary outcomes

Adverse Events related to Study Treatment
Time frame: Up to 48 months
Overall Survival (OS)
Time frame: Up to 48 months
Progression Free Survival (PRS)
Time frame: Up to 48 months
Duration of Response
Time frame: Up to 48 months
Response per Immune-related response criteria (irRECIST)
Time frame: Up to 48 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2025.
Individual participant dataSharing planned: No

Related trials for Renal Cell Carcinoma

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dan Zandberg, MD principal investigator

UPMC Hillman Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 27 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 6 Nov 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?

This study is still under way. Results are not available in the source record yet.

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?

Participants Experiencing a Dose Limiting Toxicity (DLT) (time frame: Up to 28 days (during first cycle of treatment)). The study lists 2 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 NCT04074967.

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 6 Nov 2025.