All participants will have cytologically or histologically confirmed stage IIIB, IIIC, IIID melanoma that can be surgically removed.

Patients will have a baseline CD8 PET scan prior to one dose of neoadjuvant nivolumab

1mg/kg + ipilimumab 3mg/kg. After 4 weeks, patients will have a repeat CD8 PET scan and then undergo surgical resection of their stage III melanoma.

PET Scan

Patients will have a baseline CD8 PET scan prior to receiving one dose of neoadjuvant nivolumab

1mg/kg + ipilimumab 3mg/kg.

Nivolumab

Ipilimumab

Surgical Resection of Melanoma

Antigen-specific CAR T, CTL and DCvac to treat melanoma.

Lung-Ji Chang, PhD

The cohort of individuals with metastatic NSCLC will be treated with the reICB regimen (anti-PD(L)-1 antibodies+ cyclophosphamide+ bevacizumab) until disease progression or unacceptable toxicity.

* ICI (one of the following): Atezolizumab 1200 mg every 3 weeks/Nivolumab 240 mg every 2 weeks/Pembrolizumab 200 mg every 3 weeks
* Cyclophosphamide 50 mg PO daily
* Bevacizumab 7.5 mg/kg every 3 weeks

reICB regimen (NSCLC)

The cohort of individuals with metastatic cutaneous melanoma will be treated with the reICB regimen (anti-PD(L)-1 antibodies+ cyclophosphamide+ bevacizumab) until disease progression or unacceptable toxicity.

* ICI (one of the following): Nivolumab 240 mg every 2 weeks/Pembrolizumab 200 mg every 3 weeks
* Cyclophosphamide 50 mg PO daily
* Bevacizumab 7.5 mg/kg every 3 weeks

reICB regimen (melanoma)

Aram A. Musaelyan, PhD

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)

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

Phase Ib ARRY-614 + nivolumab

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)

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

Participants with of NSCLC and HNSCCC will receive ARRY-614 combined with nivolumab.

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

Participants with melanoma will receive ARRY-614 combined with nivolumab + ipilimumab.

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)

Participants with RCC will receive ARRY-614 combined with nivolumab + ipilimumab.

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

On days 1 and 2 patients will be sensitized to DNP by topically applying 0.1 ml of 2% DNP dissolved in acetone-corn oil (Sigma) to the inner aspect of the arm.

On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered at the day care unit. On day 14 the appropriate dose of irradiated M20/A2B cells will be injected into three adjacent sites on the upper arm or thigh, avoiding limbs where lymph node dissection had been previously performed. Four additional doses of the vaccine will be administered at intervals of 21 days.

On days 14, 35, 56, 77 and 98 the appropriate dose of irradiated M20/A2B cells will be injected into three adjacent sites on the upper arm or thigh, avoiding limbs where lymph node dissection had been previously performed.

A2/4-1BBL melanoma vaccine

Include brand names, serial numbers and code names, if applicable. Other names are used to improve search results on the ClinicalTrials.gov web site.

On days 1 and 2 patients will be sensitized to DNP by topically applying 0.1 ml of 2% DNP dissolved in acetone-corn oil (Sigma) to the inner aspect of the arm.

DNP sensititzation

On day 10, intravenous low dose cyclophosphamide, 300 mg/m2, will be administered.

Cyclophosphamide

Hani Steinberg, RN

This study is designed for patients who had malignant melanoma and, following tumor removal, are now free of disease, or have only very minor residual disease, and are at a very high risk of disease recurrence. These patients will be treated with the A2/4-1BBL melanoma vaccine, a compatible melanoma cell line that has been engineered to express a molecule termed 4-1BBL, which enhances the chances of the cell line to be recognized by the patient's immune system, and to induce its stimulation. The hypothesis that drives the study states that the immune response against the cell line will also be effective against the residual tumor that may still be present in the body.

PET 스캔, 니볼루맙, 이필리무맙, 흑색종의 외과적 절제

흑색종을 치료하기 위한 항원 특이적 CAR T, CTL 및 DCvac.

reICB 요법(비소세포폐암), reICB 요법(흑색종)

RY-614 + 니볼루맙 + 이필리무맙, 2상 ARRY-614 + 니볼루맙, 2상 ARRY-614 + 니볼루맙 + 이필리무맙(흑색종), 2상 ARRY-614 + 니볼루맙 + 이필리무맙(신장암)

A2/4-1BBL 흑색종 백신, DNP 감작, 사이클로포스파마이드

HLA A2/4-1BB 리간드를 발현하도록 변형된 흑색종 백신