Nivolumab (Opdivo®) Plus ABI-009 (Nab-rapamycin) for Advanced Sarcoma and Certain Cancers

NCT03190174 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: SOC-1701
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the safety/toxicity and potential anti-tumor activity of sequential administration of nivolumab and escalating doses of the mammalian target of rapamycin (mTOR) inhibitor nab-rapamycin (ABI-009) in advanced Ewing's sarcoma, perivascular epithelioid cell tumor (PEComa), epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urothelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, high microsatellite instability (MSI-H)/ mismatch repair deficient (dMMR) metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors.

Conditions

Ewing Sarcoma; PEComa; Epithelioid Sarcoma; Desmoid Tumor; Chordoma; Non Small Cell Lung Cancer; Urothelial Carcinoma; Melanoma; Renal Cell Carcinoma; Squamous Cell Carcinoma; Hepatocellular Carcinoma; Classical Hodgkin Lymphoma; Colorectal Cancer; MTOR Activating Mutation

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of ABI-009

  The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced dose-limiting toxicity (DLT), with the next higher dose level having at least two patients who experienced DLT.

  Week 6

Secondary Outcomes (3)

• Disease Control Rate

  12 weeks

• Progression Free Survival

  24 weeks

• Overall Survival

  30 weeks

Study Arms (1)

Arm 1

EXPERIMENTAL

This is an open label, dose-seeking phase 1b study using a defined dose of nivolumab and escalating doses of Nab-Rapamycin (ABI-009) given intravenously. I. Dose Escalation Phase 1 Part of Study: The study will employ the standard "cohort of three" design. No intra-patient dose escalation will take place. II. Expansion Phase 1b Part of Study: Following dose escalation, an additional 22-28 patients will receive ABI-009 at the MTD and defined doses of nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients in the expansion phase of the study may continue treatment up to 18 three-week cycles or until significant disease progression or unacceptable toxicity occurs.

Drug: Nab-Rapamycin; Biological: Nivolumab

Interventions

Nab-Rapamycin DRUG

Escalating doses of ABI-009 will be given IV over 30 min for 2 of every 3 weeks beginning Day 8 Cycle 2. Only nivolumab will be given in Cycle 1. At Dose Level 1, 3-6 patients will receive 56 mg/m\^2; at Dose Level 2, 3-6 six patients will receive 75 mg/m\^2; and at Dose Level 3, 3-6 patients will receive 100 mg/m\^2.

Also known as: ABI-009

Arm 1

Nivolumab BIOLOGICAL

A defined dose of nivolumab, 3 mg/kg, will be given IV over 30 minutes q 3 weeks

Also known as: Opdivo

Arm 1

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically confirmed diagnosis of Ewing's sarcoma, PEComa, epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urothelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, MSI-H/dMMR metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors, that is either metastatic or locally advanced and for which surgery is not a recommended option.
• Patients must have one or more measurable target lesions by CT scan or MRI. Measurable disease by RECIST v1.1.
• Patients must not have been previously treated with a PD-1 inhibitor in combination with an mTOR inhibitor.
• Prior treatment (investigational or other), chemotherapy, radiotherapy, surgery, or other therapeutic agents (except immunotherapy and mTOR inhibitors) is allowed, if completed after 5 half-lives or ≥28 days prior to enrollment, whichever is shorter.
• Eligible patients, 12 years or older, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients must have the following blood chemistry levels at screening (obtained ≤14 days prior to enrollment (local laboratory):
• total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dl
• Aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if attributable to liver metastases)
• serum creatinine ≤1.5 x ULN
• Adequate biological parameters as demonstrated by the following blood counts at screening (obtained ≤14 days prior to enrollment, local laboratory):
• Absolute neutrophil count (ANC) ≥1.5 × 109/L;
• Platelet count ≥100,000/mm3 (100 × 109/L);
• Hemoglobin ≥9 g/dL.
• Serum triglyceride \<300 mg/dL; serum cholesterol \< 350 mg/dL.
• Male or non-pregnant and non-breast feeding female:

You may not qualify if:

• Concurrent or prior immunotherapy with a PD-1 inhibitor in combination with an mTOR inhibitor.
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A patient with controlled and asymptomatic CNS metastases may participate in this study. As such, the patient must have completed any prior treatment for CNS metastases ≥28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.
• Active gastrointestinal bleeding.
• Pre-existing thyroid abnormality is allowed provided thyroid function can be controlled with medication.
• Uncontrolled serious medical or psychiatric illness. Patients with a "currently active" second malignancy other than non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pT2 with Gleason Score ≤ 6 and postoperative prostate-specific antigen (PSA) \<0.5 ng/mL), or other adequately treated carcinoma-in-situ are ineligible. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥1 year).
• Liver-directed therapy within 2 months of enrollment. Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cryotherapy/ablation) is allowed if these therapies did not affect the areas of measurable disease being used for this protocol.
• Recent infection requiring systemic anti-infective treatment that was completed ≤14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection).
• Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy.
• Unstable coronary artery disease or myocardial infarction during preceding 6 months.
• Receiving any concomitant antitumor therapy.
• Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
• Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfenadine) within the 14 days prior to receiving the first dose of ABI-009.
• Known Human Immunodeficiency Virus (HIV).
• Active Hepatitis B or Hepatitis C.
• Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks of trial enrollment

Sponsors & Collaborators

• Sarcoma Oncology Research Center, LLC: lead
• Aadi Bioscience, Inc.: collaborator

Study Sites (1)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Related Publications (2)

• Gonzalez-Angulo AM, Meric-Bernstam F, Chawla S, Falchook G, Hong D, Akcakanat A, Chen H, Naing A, Fu S, Wheler J, Moulder S, Helgason T, Li S, Elias I, Desai N, Kurzrock R. Weekly nab-Rapamycin in patients with advanced nonhematologic malignancies: final results of a phase I trial. Clin Cancer Res. 2013 Oct 1;19(19):5474-84. doi: 10.1158/1078-0432.CCR-12-3110.

  PMID: 24089446 RESULT

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Sarcoma, Ewing; Perivascular Epithelioid Cell Neoplasms; Sarcoma; Desmoid Tumors; Chordoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Melanoma; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Carcinoma, Hepatocellular; Colorectal Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Germ Cell and Embryonal; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Squamous Cell; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The study was completed with a small number of subjects analyzed.

Results Point of Contact

• Title: Erlinda M. Gordon, MD/Principal Investigator
• Organization: Sarcoma Oncology Research Center

egordon@sarcomaoncology.com

310-552-9999

Study Officials

• Erlinda M Gordon, MD

  Sarcoma Oncology Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: June 16, 2017
• Study Start: August 24, 2017
• Primary Completion: December 1, 2021
• Study Completion: December 2, 2021
• Last Updated: February 17, 2025
• Results First Posted: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)