Trial of dostarlimab (TSR-042) for patients with high-risk locally advanced cervical cancer after chemo-radiation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Grupo Espanol De Investigacion En Cancer De Ovario

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Jun 2019 → ongoing

Decision date (initial)

2024-03-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GSK

External identifiers

EU CT number

2023-510268-11-00

EudraCT number

2018-002155-15

ClinicalTrials.gov

NCT03833479

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Evaluate the progression-free survival (PFS) of patients with high risk locally advanced cervical cancer (HRLACC) who have achieved a partial (PR) or complete response (CR) after concurrent hemotherapy and radiation therapy (CCRT) and received dostarlimab as maintenance therapy.

Secondary objectives 3

1. - Determine the frequency and severity of adverse events (AEs) as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for dostarlimab administered on this study.
2. - Evaluate the overall survival (OS) of subjects with HRLACC who have received dostarlimab in the maintenance setting following concurrent chemotherapy and radiation therapy.
3. Evaluate patient reported outcomes (PROs) of: o Health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) and EQ-5D-5L, o Fatigue as measured by the PROMIS-Cancer-Fatigue Short Form 4a, and o Pain as measured by a single item of the Brief Pain Inventory (BPI).

Conditions and MedDRA coding

Cervical cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Signed informed consent before any study-specific procedure.
2. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
3. Participant must be a female ≥ 18 years of age.
4. Life expectancy ≥3 months.
5. Participant must have biopsy-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix.
6. Patients must have archival tumor tissue available that is formalinfixed and paraffin embedded.
7. At diagnosis: • FIGO 2009 stages IB2, IIA2, IIB with pelvic lymph node involvement. • FIGO 2009 stages IIIA, IIIB, IVA. • Any FIGO 2009 stage with para-aortic lymph node involvement
8. Subjects must have received combination chemotherapy and radiotherapy (CCRT) with curative intent. Patients must have received at least 4 doses of weekly cisplatin.
9. Patients must had achieved a partial (PR) or a complete response (CR) after concurrent chemo-radiation therapy (CCRT).
10. Patients must have completed definitive treatment, namely chemoradiation, up to 12 weeks prior to sign the Informed Consent form.
11. Toxicities resulting from chemo-radiation must resolve to ≤ Grade 1 prior to randomization.
12. Participant must have adequate organ function, defined as follows: - Absolute neutrophil count ≥ 1,500/μL - Platelets ≥ 100,000/μL - Hemoglobin ≥ 9 g/dL - Serum creatinine ≤ 1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN - Total bilirubin ≤ 1.5× ULN OR direct bilirubin ≤ 1× ULN - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN - International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN. Activated partial thromboplastin time (aPTT) ≤1.5× ULN
13. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
14. Negative Test Results for Hepatitis
15. Female participant has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 150 days after the last dose of study treatment, or is of nonchildbearing potential.of nonchildbearing potential.
16. Participant must agree to not breastfeed during the study or for 150 days after the last dose of study treatment
17. Male partners must agree to use an adequate method of contraception starting with the first dose of study treatment through 150 days after the last dose of study treatment.
18. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.

Exclusion criteria 27

1. Histological types other than in inclusion criteria, like sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers
2. FIGO 2009 Stage IVB
3. 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.
4. Has not achieved at least a partial response by RECIST v1.1 after completion of CCRT administered with curative intent.
5. Patients previously treated with chemotherapy except when used concurrently with radiation therapy
6. Prior treatment with any anti-VEGF drug, including bevacizumab, CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
7. Patients with a concomitant malignancy other than non-melanoma skin cancer.
8. History of autoimmune disease
9. History of idiopathic pulmonary fibrosis, organizing pneumonia, druginduced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
10. History of interstitial lung disease.
11. Active tuberculosis.
12. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
13. 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.
14. Treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.
15. Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1.
16. Women that are breastfeeding or pregnant.
17. Demonstration of any other disease, neurological or metabolic dysfunction, found upon physical examination or laboratory tests involving a reasonable suspicion of the existence of a disease or condition that contraindicates the use of an experimental drug, or that involves an increased risk to the patient of treatment-related complications.
18. No medical or psychiatric illness that may impede the performance of a systemic or surgical treatment.
19. Participant must not be simultaneously enrolled in any interventional clinical trial.
20. Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
21. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
22. Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
23. Participant must not have a known hypersensitivity to dostarlimab components or excipients.
24. Participant must not have a serious, uncontrolled medical disorder or nonmalignant systemic disease.
25. Participant must not have known, symptomatic brain or leptomeningeal metastases.
26. Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
27. Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS)

Secondary endpoints 4

1. Overall survival (OS)
2. Health-related quality of life (HRQOL) measure by the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) and EQ-5D-5L.
3. Fatigue measure by the PROMIS-Cancer-Fatigue Short Form 4a
4. Pain measure by a single item of the Brief Pain Inventory (BPI).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Grupo Espanol De Investigacion En Cancer De Ovario

Sponsor organisation

Grupo Espanol De Investigacion En Cancer De Ovario

Address

Calle De Santa Engracia 151 Planta 5ª Oficina 2

City

Madrid

Postcode

28003

Country

Spain

Scientific contact point

Organisation

Grupo Espanol De Investigacion En Cancer De Ovario

Contact name

APICES SOLUCIONES S.L, Clinical Operations Department

Public contact point

Organisation

Grupo Espanol De Investigacion En Cancer De Ovario

Contact name

APICES SOLUCIONES S.L, Clinical Operations Department

Third parties 1

Locations

1 EU/EEA country · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications