Agnostic Therapy in Rare Solid Tumors (ANTARES)

April 10, 2026 updated by: Paulo Marcelo Gehn Hoff, Instituto do Cancer do Estado de São Paulo

Phase II Basket Study to Evaluate the Tissue-agnostic Efficacy of Anti-Programmed Cell Death Protein 1 (Anti-PD1) Monoclonal Antibody in Patients With Advanced Rare Tumors

The ANTARES study is a phase II basket trial designed to evaluate the tissue-agnostic efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or metastatic rare tumors.

The study aims to treat rare malignancies with PD-L1 expression (CPS ≥ 10), regardless of the tumor's tissue type or location. Patients who have not responded to standard treatments will be included, and treatment will last for up to 12 months. The study will assess objective response, progression-free survival, and biomarkers such as PD-L1, ctDNA, and microvesicles, in a multicenter collaborative effort to provide innovative therapeutic options for this underrepresented population

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The ANTARES study is a phase II "basket" trial designed to evaluate the tissue-agnostic efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or metastatic rare tumors. A "basket" trial is an innovative type of clinical trial where patients with different types of cancers, but sharing a common molecular feature (in this case, PD-L1 expression), are treated with the same therapy, regardless of the tumor's site of origin. This approach allows for the evaluation of treatments targeting specific molecular characteristics, independent of the primary cancer type.

Rare tumors, as defined by the World Health Organization (WHO), have an incidence of fewer than six cases per 100,000 people per year. Although each rare cancer type is individually uncommon, collectively they account for 25-30% of all malignancies and are often underrepresented in clinical trials due to recruitment challenges and limited funding. As a result, patients with rare cancers generally have a poorer prognosis compared to those with more common tumors.

In this study, patients with advanced or refractory rare malignancies expressing PD-L1, with a combined positive score (CPS) of ≥10, will be treated with nivolumab. Treatment will be administered until disease progression or for a maximum duration of 12 months, aiming to assess the efficacy and safety of this tissue-agnostic immunotherapy approach. Efficacy will be measured according to RECIST v1.1 criteria, with objective response as the primary endpoint. Additionally, the study will assess response biomarkers, including PD-L1, circulating tumor DNA (ctDNA), and microvesicles, to better understand the correlation between biomarker expression and clinical outcomes.

This multicenter trial, with an estimated duration of four years, will be conducted at Institute of Cancer of the State of São Paulo (ICESP) and other partner institutions. The study aims to overcome existing barriers in rare cancer treatment by offering an innovative approach that explores the potential of personalized therapies based on molecular characteristics, rather than the tumor's primary site

Study Type

Interventional

Enrollment (Estimated)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • Brasília, Brazil, 70390-903
      • Rio de Janeiro, Brazil, 22281-100
        • Not yet recruiting
        • Instituto D'Or de Pesquisa e Ensino
        • Contact:
        • Contact:
    • Ceará
    • Estado de Bahia
    • Paraná
    • Pernambuco
      • Recife, Pernambuco, Brazil, 52010-010
        • Not yet recruiting
        • IDOR Recife
        • Contact:
          • Rafael CA Lima, Doctor
          • Phone Number: +55 81 3131-7800
          • Email: cep@idor.org
        • Contact:
    • São Paulo
      • São Paulo, São Paulo, Brazil, 04.501-000
      • São Paulo, São Paulo, Brazil, 05403-010
        • Recruiting
        • Instituto do Câncer do Estado de São Paulo - ICESP
        • Contact:
        • Contact:
        • Principal Investigator:
          • Camila MV Moniz, Doctor
        • Sub-Investigator:
          • Raelson Miranda, Doctor
        • Sub-Investigator:
          • Renata RC Bonádio, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Age 18 years or older.
  2. Patients with immunohistochemistry for PD-L1 with a combined positive score (CPS) of 10 or higher.
  3. Patients with progression or intolerance to already approved and accessible treatments for the specific neoplasm and population.
  4. Documented disease progression radiologically after the last routine treatment.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Measurable lesion per RECIST v1.1. Lesions previously treated with radiotherapy can only be used as target lesions if they are confirmed to be progressing by imaging before enrollment.

  7. Male participants must meet at least one of the following conditions:

    1. Considered infertile;
    2. No fertile partner;

    3. Has a fertile partner who agrees to follow contraceptive guidance throughout the study period and for at least 6 months after the last dose of Nivolumab;

      and

    4. Agrees to abstain from sperm donation throughout the study period and for at least 6 months after the last dose of Nivolumab.

  8. Female participants must meet at least one of the following conditions:

    1. Considered infertile;
    2. Agrees to follow contraceptive guidance throughout the study period and for at least 6 months after the last dose of Nivolumab;
  9. Estimated life expectancy greater than 12 weeks, as determined by the investigator or delegated sub-investigator.

  10. Preserved organ functions defined by:

    • Absolute neutrophil count ≥ 1,000;
    • Hemoglobin ≥ 8.0 g/dL (patients may receive transfusions to reach this level);
    • Platelet count ≥ 100,000;
    • Total bilirubin ≤ 1.5 × Upper Limit of Normal (ULN), or ≤ 3.0 × ULN for patients with Gilbert's syndrome;
    • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN in the presence of liver metastases);
    • Creatinine clearance > 30 mL/min (estimated by Cockcroft-Gault).

  11. Diagnosis of rare cancer (List I) confirmed by histopathological examination, with the possibility of including other types of rare tumors (incidence of less than 6 in every 100,000) after careful evaluation and approval by the study board.

    • List I:

      • Urachal adenocarcinoma
      • Parathyroid carcinoma
      • Nasopharyngeal epithelial tumors
      • Fibrolamellar carcinoma of any primary site
      • Angiosarcoma of any primary site
      • Secretory breast carcinoma
      • Anal cancer
      • Metaplastic breast carcinoma
      • Chromophobe renal carcinoma, Microphthalmia-associated Transcription Factor (MiT) family translocation renal carcinoma; renal carcinoma with Fumarate Hydratase (FH) or Succinate Dehydrogenase (SDH) deficiency
      • Carcinosarcoma of any primary site
      • Small intestine cancer
      • Cholangiocarcinoma
      • Sertoli-Leydig cell tumors
      • Cervical cancer of non-epidermoid histology
      • Tracheal epithelial tumors
      • Non-cystadenoma salivary gland tumors
      • Mesothelioma of any site
      • Neuroblastoma
      • Adrenal cancer
      • Penile cancer
      • Apocrine carcinoma
      • Fibrosarcoma of any primary site
      • Cancer of unknown primary site
      • Hemangioblastoma of any primary site
      • Thyroid cancer
      • Hepatoblastoma
      • Fallopian tube cancer
      • Leiomyosarcoma of any primary site
      • Vaginal cancer
      • Neurofibrosarcoma of any primary site
      • Gallbladder cancer
      • Osteosarcoma of any primary site
      • Bile duct cancer
      • Clear cell endometrial carcinoma
      • Yolk sac tumor of any primary site
      • Non-epidermoid bladder cancer
      • Vulvar cancer
      • Kaposi's sarcoma
      • Epithelial ovarian cancer
      • Soft tissue sarcoma
      • Urethral cancer
      • Granulosa cell tumor of any primary site
      • Cystadenoma carcinoma
      • Primitive neuroectodermal tumor of any primary site
      • Pure or mixed neuroendocrine tumors with neuroendocrine component
      • Trophoblastic tumor

Exclusion Criteria

  1. Previous treatment lines with immunotherapy (immune checkpoint inhibitors).
  2. Pregnant or breastfeeding individuals.
  3. Limiting comorbidity, in the opinion of the investigator.
  4. Active infection.
  5. Major surgery within the last 4 weeks.
  6. Functional class II or greater heart failure.
  7. Myocardial infarction or stroke within the last 6 months.
  8. History of pulmonary fibrosis or pneumonitis.
  9. Autoimmune diseases, except for patients with vitiligo and/or controlled thyroid/hypothyroidism without the use of immunosuppressors.
  10. Second invasive primary tumor diagnosed in the last 3 years and/or with active disease, except for localized skin tumors (non-melanoma) that have been treated with curative intent.
  11. Patients with prolonged QT interval.
  12. Uncontrolled Central Nervous System (CNS) metastases. Patients who have previously received local treatment, such as radiotherapy, will be eligible if clinical and radiological stability is demonstrated in the 2 weeks prior to the start of treatment. Patients must not be using corticosteroids for managing CNS disease.
  13. Presence of meningeal carcinomatosis.
  14. Worsening renal and liver function in the 14 days prior to enrollment.
  15. History of solid organ transplantation with or without immunosuppression.
  16. Patients with untreated acquired immunodeficiency. Immunocompromised patients may be included as long as they do not have active opportunistic disease and/or active infection, after thorough clinical evaluation by the investigator or sub-investigator. HIV-positive patients must have documented undetectable viral load prior to inclusion.
  17. Chronic use of corticosteroids at doses greater than 10 mg/day of prednisone or equivalent. Patients with adrenal insufficiency of non-autoimmune etiology (e.g., previous bilateral adrenalectomy) may be included if they are clinically compensated with 10 mg/day of prednisone or equivalent or less.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single-Arm Efficacy Study
Treatment will be administered with intravenous nivolumab at a dose of 480 mg every 4 weeks. Treatment will continue until limiting toxicity, disease progression, or for a maximum of 12 months as maintenance if the individual achieves stable disease, partial response, or complete response.
Drug: Nivolumab

The intervention consists of administering Nivolumab 480 mg intravenously every 4 weeks, with a +5 day window for postponement but not for advancement of treatment. Treatment will continue until limiting toxicity, disease progression, or for a maximum period of 12 months (13 cycles) as maintenance therapy, provided the patient maintains stable disease, a partial response, or a complete response. Patients who are off treatment for more than 56 days (2 cycles) due to Nivolumab-related toxicities or other clinical issues will be discontinued from the protocol.

After 12 months of treatment or in the event of study discontinuation for any reason, patients will be followed by the research team via telephone every 60 days, with a +/- 7 day window, until death.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Objective
Time Frame: 2 years
Overall survival (in months) of patients with advanced or metastatic rare malignancies and CPS ≥ 10 following disease progression after prior treatments while receiving the anti-PD1 antibody Nivolumab.
2 years
Primary Endpoint
Time Frame: 2 years

The primary outcome of the study is the disease control rate (DCR) based on imaging, considering the best response to treatment. A response rate of 5% will be considered non-promising, and a response rate of 25% will be considered promising. The study follows Simon's two-stage design, with type I error (alpha) set at 0.05 and type II error (beta) at 0.10. In the first stage, if at least 1 out of the first 9 participants achieves disease control (stable disease, partial response, or complete response), 16 additional participants will be recruited for the second stage.

The study will be deemed positive if at least 3 out of 25 participants achieve disease control (partial response, complete response, or stable disease). A 10% drop-out rate (3 participants) is anticipated, bringing the maximum total recruitment to 28 participants.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 2 years
Percentage of patients with a tumor size reduction, measured according to RECIST criteria.
2 years
Subgroup Analysis Based on PD-L1 Expression and CPS:
Time Frame: 2 years
PD-L1 Expression: Proportion of patients showing PD-L1 positivity. CPS Subgroups: Proportion of patients with CPS between 10-20 and those with CPS > 20.
2 years
Correlation of Clinical Outcomes with Biomarker Assessments
Time Frame: 2 years

Microvesicle Analysis: Correlation between clinical outcomes and levels of circulating microvesicles.

Serum Multiplex Panel: Correlation between clinical outcomes and serum biomarker levels (e.g., cytokines, chemokines), measured in concentration units (e.g., pg/mL).
2 years
Overall Survival (OS)
Time Frame: 2 years
Time from treatment initiation to death from any cause, measured in months.
2 years
Progression-Free Survival (PFS)
Time Frame: 2 years
Time from treatment initiation to disease progression or death, whichever occurs first, measured in months.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto do Cancer do Estado de São Paulo

Collaborators

Financiadora de Estudos e Projetos

Investigators

  • Principal Investigator: Camila MV Moniz, Doctor, Oncologist

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 16, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

October 3, 2024

First Submitted That Met QC Criteria

October 10, 2024

First Posted (Actual)

October 15, 2024

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NP4021/2023
  • 68590423.0.1001.0068 (Registry Identifier: Certificate of Ethical Review Submission)
  • 01.23.0265.00 (Other Grant/Funding Number: FINEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

It has been decided not to share individual participant data (IPD) related to the study for several reasons. Protecting the privacy of participants is a priority. Sharing IPD may expose sensitive information that, even when de-identified, can be traced back to individuals.

Furthermore, the complexity of the data makes sharing challenging without the risk of misunderstandings or misinterpretations, which could compromise the integrity of the research. Sharing IPD without the explicit consent of participants may violate ethical principles of respect and protection.

There is also a need to comply with regulatory guidelines governing data sharing to avoid potential legal issues. Finally, the focus will be on disseminating aggregated results that can benefit the scientific community and the public without compromising individual privacy.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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