Agnostic Therapy in Rare Solid Tumors
ANTARES
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
3 other identifiers
interventional
28
1 country
8
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jul 2024
Typical duration for phase_2
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 16, 2024
CompletedFirst Submitted
Initial submission to the registry
October 3, 2024
CompletedFirst Posted
Study publicly available on registry
October 15, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2028
April 15, 2026
April 1, 2026
2 years
October 3, 2024
April 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Primary Objective
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
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 Outcomes (5)
Objective Response Rate (ORR)
2 years
Subgroup Analysis Based on PD-L1 Expression and CPS:
2 years
Correlation of Clinical Outcomes with Biomarker Assessments
2 years
Overall Survival (OS)
2 years
Progression-Free Survival (PFS)
2 years
Study Arms (1)
Single-Arm Efficacy Study
EXPERIMENTALTreatment 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- Age 18 years or older.
- Patients with immunohistochemistry for PD-L1 with a combined positive score (CPS) of 10 or higher.
- Patients with progression or intolerance to already approved and accessible treatments for the specific neoplasm and population.
- Documented disease progression radiologically after the last routine treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- 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.
- Male participants must meet at least one of the following conditions:
- Considered infertile;
- No fertile partner;
- 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
- Agrees to abstain from sperm donation throughout the study period and for at least 6 months after the last dose of Nivolumab.
- Female participants must meet at least one of the following conditions:
- Considered infertile;
- Agrees to follow contraceptive guidance throughout the study period and for at least 6 months after the last dose of Nivolumab;
- +56 more criteria
You may not qualify if:
- Previous treatment lines with immunotherapy (immune checkpoint inhibitors).
- Pregnant or breastfeeding individuals.
- Limiting comorbidity, in the opinion of the investigator.
- Active infection.
- Major surgery within the last 4 weeks.
- Functional class II or greater heart failure.
- Myocardial infarction or stroke within the last 6 months.
- History of pulmonary fibrosis or pneumonitis.
- Autoimmune diseases, except for patients with vitiligo and/or controlled thyroid/hypothyroidism without the use of immunosuppressors.
- 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.
- Patients with prolonged QT interval.
- 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.
- Presence of meningeal carcinomatosis.
- Worsening renal and liver function in the 14 days prior to enrollment.
- History of solid organ transplantation with or without immunosuppression.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
Hospital São Carlos
Fortaleza, Ceará, 60170-170, Brazil
Hospital São Rafael
Salvador, Estado de Bahia, 41253-190, Brazil
Hospital Santa Cruz
Curitiba, Paraná, 80420-090, Brazil
IDOR Recife
Recife, Pernambuco, 52010-010, Brazil
Instituto D'or de Pesquisa e Ensino
São Paulo, São Paulo, 04.501-000, Brazil
Instituto do Câncer do Estado de São Paulo - ICESP
São Paulo, São Paulo, 05403-010, Brazil
DF Star
Brasília, 70390-903, Brazil
Instituto D'Or de Pesquisa e Ensino
Rio de Janeiro, 22281-100, Brazil
Related Publications (8)
Bogaerts J, Sydes MR, Keat N, McConnell A, Benson A, Ho A, Roth A, Fortpied C, Eng C, Peckitt C, Coens C, Pettaway C, Arnold D, Hall E, Marshall E, Sclafani F, Hatcher H, Earl H, Ray-Coquard I, Paul J, Blay JY, Whelan J, Panageas K, Wheatley K, Harrington K, Licitra L, Billingham L, Hensley M, McCabe M, Patel PM, Carvajal R, Wilson R, Glynne-Jones R, McWilliams R, Leyvraz S, Rao S, Nicholson S, Filiaci V, Negrouk A, Lacombe D, Dupont E, Pauporte I, Welch JJ, Law K, Trimble T, Seymour M. Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative. Eur J Cancer. 2015 Feb;51(3):271-81. doi: 10.1016/j.ejca.2014.10.027. Epub 2014 Dec 24.
PMID: 25542058BACKGROUNDCortes J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi: 10.1056/NEJMoa2115022.
PMID: 35320644BACKGROUNDDuBois SG, Laetsch TW, Federman N, Turpin BK, Albert CM, Nagasubramanian R, Anderson ME, Davis JL, Qamoos HE, Reynolds ME, Cruickshank S, Cox MC, Hawkins DS, Mascarenhas L, Pappo AS. The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer. 2018 Nov 1;124(21):4241-4247. doi: 10.1002/cncr.31701. Epub 2018 Sep 11.
PMID: 30204247BACKGROUNDLe DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.
PMID: 26028255BACKGROUNDLi BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazieres J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Perol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Janne PA; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251. doi: 10.1056/NEJMoa2112431. Epub 2021 Sep 18.
PMID: 34534430BACKGROUNDMarabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, Chung HC, Kindler HL, Lopez-Martin JA, Miller WH Jr, Italiano A, Kao S, Piha-Paul SA, Delord JP, McWilliams RR, Fabrizio DA, Aurora-Garg D, Xu L, Jin F, Norwood K, Bang YJ. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020 Oct;21(10):1353-1365. doi: 10.1016/S1470-2045(20)30445-9. Epub 2020 Sep 10.
PMID: 32919526BACKGROUNDMok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. doi: 10.1016/S0140-6736(18)32409-7. Epub 2019 Apr 4.
PMID: 30955977BACKGROUNDSchmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.
PMID: 32101663BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Camila MV Moniz, Doctor
Oncologist
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Full Professor of Clinical Oncology in the Department of Radiology and Oncology at FMUSP (University of São Paulo Medical School).
Study Record Dates
First Submitted
October 3, 2024
First Posted
October 15, 2024
Study Start
July 16, 2024
Primary Completion (Estimated)
July 1, 2026
Study Completion (Estimated)
May 1, 2028
Last Updated
April 15, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share
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.