TSR-042 as Maintenance Therapy for Patients With High-risk Locally Advanced Cervical Cancer After Chemo-radiation

NCT03833479 | Active Not Recruiting Phase 2

• 3 other identifiers: GEICO 78-C (ATOMICC)2023-510268-11-002018-002155-15
• Study Type: interventional
• Target: 134
• Locations: 2 countries
• Sites: 29

Brief Summary

Patients with locally advanced cervical cancer (LACC) despite definitive chemo-radiotherapy, has a poor progression-free survival (PFS) and overall survival (OS). The hypothesis is that the use of TSR-042, checkpoint inhibitor, as consolidation therapy following concurrent chemo-radiation would increase PFS in these patients. The incorporation of immunotherapy after chemo-radiation is one the best scenarios for this approach, since takes advantages of "the ideal microenvironment" created after radiation. In a similar rationale, the phase 3 study that compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy, showed that progression-free survival was significantly longer with durvalumab than with placebo in all sub-groups regardless of response obtained to chemotherapy, namely patients with stable disease (SD) gained the same benefit that patients with partial response (PR). Due to the aforementioned biology of cervical cancer, the proven activity of anti programmed cell death protein 1 (Anti-PD1) agents in metastatic and/or recurrent cervical cancer and the poor PFS and OS in patients with LACC despite definitive chemo-radiotherapy, we consider to analyze the Anti-PD1 agent, TSR-042 as maintenance therapy after concurrent chemo-radiation (CCRT)

Conditions

Cervical Cancer; Advanced Cancer

Keywords

TSR-042; Anti-PD1; advanced cervical cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Time from the date of randomization to the date of first documentation of disease progression or death due to any cause, whichever occurs first based on investigator assessment using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)

  30 months

Secondary Outcomes (6)

• Frequency and severity of adverse events (AEs)

  30 months

• Overall survival (OS)

  30 months

• Patient reported outcomes (PROs) of health-related quality of life (HRQOL)

  30 months

• Patient reported outcomes (PROs) of health-related quality of life (HRQOL)

  30 months

• Patient reported outcomes (PROs) of fatigue

  30 months

Study Arms (2)

No further treatment

EXPERIMENTAL

No further treatment

Other: No Further Treatment

TSR-042

EXPERIMENTAL

TSR-042 treatment administered using a 30 -minute IV infusion (with a -5 minute and +15 minute window permitted).

Drug: TSR-042

Interventions

No Further Treatment OTHER

No further treatment

No further treatment

TSR-042 DRUG

Fixed 500 mg TSR-042 dose Q3W for the first 4 doses followed by a fixed 1000 mg TSR-042 dose Q6W for up to 24 months

TSR-042

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent before any study-specific procedure
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Participant must be a female ≥ 18 years of age
• Life expectancy ≥3 months
• Participant must have biopsy-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix.
• Patients must have archival tumor tissue available that is formalin-fixed and paraffin embedded.
• At diagnosis:
• Federation of Gynecologists and Obstetricians (FIGO) stages IB2, IIA2, IIB with pelvic lymph node involvement: Biopsy-proven pelvic node involvement, 2 or more positive nodes by magnetic resonance imaging (MRI) or computed tomography (CT) (≥1.5 cm shortest dimension), 2 or more positive nodes by Positron Emission Tomography (PET) (with standardized uptake values (SUV) ≥2.5)
• FIGO stages IIIA, IIIB, IVA
• Any FIGO stage with para-aortic lymph node involvement: Biopsy-proven para-aortic node involvement, 1 or more positive nodes by MRI or CT (≥1.5 cm shortest dimension), 1 or more positive pelvic nodes by PET (with SUV ≥ 2.5)
• Subjects must have received combination chemotherapy and radiotherapy (CCRT) with curative intent. Patients must have received at least 4 doses of weekly cisplatin.
• Patients must have completed definitive treatment, namely chemo-radiation, up to 12 weeks prior to sign the Informed Consent form.
• Toxicities resulting from chemo-radiation must resolve to ≤ Grade 1 prior to randomization.
• Participant must have adequate organ function, defined as follows:
• Absolute neutrophil count ≥ 1,500/µL

You may not qualify if:

• FIGO Stage IVB (cancer has spread distantly).
• Subjects who have undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy.
• Has not achieved at least a partial response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after completion of CCRT administered with curative intent.
• Patients previously treated with chemotherapy except when used concurrently with radiation therapy. Patients who have received either concurrent paclitaxel with radiation therapy or carboplatin/paclitaxel as adjuvant therapy are ineligible for the study.
• Prior treatment with any anti-vascular endothelial growth factor (anti-VEGF) drug, including bevacizumab, CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
• Patients with a concomitant malignancy other than non-melanoma skin cancer.
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia , drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• History of interstitial lung disease.
• Active tuberculosis.
• Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
• Administration of a live, attenuated vaccine within 14 days before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
• Treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.
• Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1.
• Women that are breastfeeding or pregnant.

Sponsors & Collaborators

• Grupo Español de Investigación en Cáncer de Ovario: lead
• Apices Soluciones S.L.: collaborator
• GSK/TESARO: collaborator

Study Sites (29)

Hospital General Universitario de Elche

Elche, Alicante, Spain

Location

Hospital Universitario Donostia- Donostia Unibertsitate Ospitalea

Donostia / San Sebastian, Gipuzkoa, 20014, Spain

Location

ICO Girona

Girona, Girona, 17007, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

Location

Hospital Álvaro Cunqueiro

Vigo, Pontevedra, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Sevilla, Spain

Location

Instituto Valenciano de Oncología

Valencia, Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital La Fe

Valencia, Valencia, 46026, Spain

Location

H Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic

Barcelona, Spain

Location

H Reina Sofía Cordoba

Córdoba, 14004, Spain

Location

ICO Hospitalet

Hospitalet Del Llobregat, Spain

Location

Clinica Universitaria de Navarra

Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Virgen de la Victoria

Málaga, Spain

Location

Hospital Clinico Universitario Virgen Arrixaca

Murcia, Spain

Location

Hospital Universitario Morales Meseguer

Murcia, Spain

Location

Hospital Son Espases

Palma de Mallorca, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Spain

Location

H. Parc Taulí

Sabadell, 08208, Spain

Location

Hospital Marqués de Valdecilla

Santander, Spain

Location

Hospital de Terrassa

Terrassa, Spain

Location

Ankara Oncology Training and Research Hospital

Ankara, Anadolu Bölgesi, 06200, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, Anadolu Bölgesi, 06800, Turkey (Türkiye)

Location

Hacettepe University

Ankara, Anadolu Bölgesi, 06800, Turkey (Türkiye)

Location

Acibadem Maslak Hospital

Istanbul, Sarıyer, 34457, Turkey (Türkiye)

Location

Related Publications (1)

• Garcia-Duran C, Grau F, Villacampa G, Oaknin A. ATOMICC trial: a randomized, open-label, phase II trial of anti-PD1, dostarlimab, as maintenance therapy for patients with high-risk locally advanced cervical cancer after chemoradiation. Int J Gynecol Cancer. 2022 Sep 6;32(9):1196-1200. doi: 10.1136/ijgc-2022-003370.

  PMID: 35444013 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Ana Oaknin, PhD

  Hospital Vall d'Hebron

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: February 7, 2019
• Study Start: June 28, 2019
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

TU (4); ES (25)