Phase II Study of Durvalumab(MEDI4736) + Tremelimumab in Pulmonary Sarcomatoid Carcinoma

Phase II Study of Durvalumab +/- Tremelimumab in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

Phase II study of Durvalumab+/- Tremelimumab in patients with recurred metastatic head and neck squamous cell carcinoma

Study Overview

• Status: Completed
• Conditions: Head and Neck Neoplasms; HNSCC
• Intervention / Treatment: Drug: Durvalumab,Tremelimumab

Detailed Description

Open, multicenter, single arm, phase II, biomarker driven umbrella trial for head and neck squamous cell carcinoma

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Recurrent or metastatic HNSCC, regardless of PD-L1 or HPV status 2. Age ≥20 3. ECOG PS 0-1 4. Ineligibility for local therapy (surgery or radiotherapy) 5. Prior palliative chemotherapy including platinum-based chemotherapy. When recurred within 6 months of definitive/neoadjuvant/adjuvant chemo- or chemoradiation, the chemotherapy is considered a line of therapy 6. At least one measurable lesion by RECIST ver 1.1 7. Adequate organ function for treatment
• Absolute neutrophil count (ANC) ≥1000 cells/mm3
• Hemoglobin: ≥ 9.0 g/dL
• Platelets ≥100,000 cells/mm3
• Estimated creatinine clearance ≥40 mL/min, or serum creatinine <1.5 x institution upper limit of normal
• Bilirubin ≤1.5 x upper limit of normal (ULN)
• AST (SGOT) ≤2.5 x ULN (5.0 x ULN if hepatic metastases)
• ALT (SGPT) ≤2.5 x ULN (5.0 x ULN if hepatic metastases) 8. 12-Lead electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention 9. The patient has provided signed informed consent

Exclusion Criteria:

• 1. Previous treatment with PD-1 or PDL-1 inhibitors 2. Nasopharyngeal carcinoma 3. Cytotoxic chemotherapy within 3 weeks of study entry; immunotherapy or investigational drug within 5 half-lives of study entry 4. Any major operation or irradiation within 4 weeks of baseline disease assessment. Palliative radiation is allowed 5. Symptomatic brain metastasis 6. Patients with known interstitial lung disease 7. Patients with uncontrolled or significant cardiovascular disease 8. Previous or concurrent malignancy (except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, thyroid cancer treated curatively) without evidence of recurrence for at least 3 years prior to study entry.

  9. Pregnant or breast-feeding women 10. Systemic immunosuppressive therapy 11. Active autoimmune disease 12. Patient who have an active systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies) (inactive HBV carrier with adequate prophylactic antiviral agent can be enrolled) 13. Body weight <30kg

  14. Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Durvalumab, tremelimumab; Durvalumab is a human immunoglobulin (Ig) G1 kappa (IgG1κ) monoclonal antibody (mAb) that blocks the interaction of PD-L1 with PD-1 on T-cells and CD80 on immune cells and is engineered to reduce antibody-dependent cell-mediated cytotoxicity.(IV class) Tremelimumab is specific for human CTLA-4; cluster of differentiation a cell surface receptor that is expressed primarily on activated T cells and acts to inhibit their activation.(IV class)

Drug: Durvalumab,Tremelimumab; Durvalumab: 1.5g Q4W plusTremelimumab: 75mg Q4W up to 4cycle then Durvalumab 750mg Q2W, till PD or unacceptable toxicity.; Other Names: Experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate (RR)	RECIST1.1	24months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
•Progression-Free Survival (PFS)	Disease progression is assessed by RECIST 1.1.	24months
•Overall Survival (OS)	Overall Survival is defined as the time from first dose to death due to any cause. Through the follow-up within 30 days after study completion or termination of the last subject, death and date of death will be checked for subject alive during treatment period	24months
•Toxicity	number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03	24months
•biomarker	NGS, nanostring technology	24months

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Korean Cancer Study Group
• Investigators: Principal Investigator: Bhumsuk Keam, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2017
• Primary Completion (Actual): February 22, 2019
• Study Completion (Actual): June 3, 2021

Study Registration Dates

• First Submitted: May 31, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Durvalumab + Tremelimumab Combination Treatment; biomarker driven umbrella trial
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab
• Other Study ID Numbers: ESR-16-12012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: anticipated as research paper

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No