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

NCT04074967 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCC 19-097
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Renal Cell Carcinoma; Melanoma; Solid Tumor; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  Up to 48 months

Secondary Outcomes (5)

• Adverse Events related to Study Treatment

  Up to 48 months

• Overall Survival (OS)

  Up to 48 months

• Progression Free Survival (PRS)

  Up to 48 months

• Duration of Response

  Up to 48 months

• Response per Immune-related response criteria (irRECIST)

  Up to 48 months

Other Outcomes (3)

• Pharmacokinetic profile of ARRY-614

  Day 1 and 15 of Cycle 1, Day 1 and 15 of Cycle 2, and Day 1 of subsequent cycles (28 day cycles); up to 3 months

• Tumor Inflammation Signature (TIS) score

  28 days prior to treatment, Day 1 of Cycle 1, Cycle 2 and subsequent cycles (28 day cycles); up to 3 months

• Pharmacodynamic profile of ARRY-614

  28 days prior to treatment, Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 3; up to 3 months

Study Arms (5)

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)

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)

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.

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.

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.

Drug: Phase II ARRY-614 + nivolumab+ipilimumab (RCC)

Interventions

Phase Ib ARRY-614 + nivolumab DRUG

ARRY-614 continuously in 4-week cycles (± 3 days). Nivolumab will be dosed according to FDA-approved dosing schedule.

Phase Ib ARRY-614 + nivolumab

Phase Ib ARRY-614 + nivolumab+ipilimumab DRUG

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 Ib ARRY-614 + nivolumab + ipilimumab

Phase II ARRY-614 + nivolumab 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.

Phase II ARRY-614 + nivolumab

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 (melanoma)

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.

Phase II ARRY-614 + nivolumab + ipilimumab (RCC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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 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.
• 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.

Sponsors & Collaborators

• Dan Zandberg: lead
• Array BioPharma: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Melanoma; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dan Zandberg, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 30, 2019
• Study Start: June 11, 2020
• Primary Completion: December 27, 2024
• Study Completion: December 31, 2025
• Last Updated: November 6, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)