Durvalumab in Combination With Tremelimumab in Subjects With Advanced Rare Solid Tumors

A Phase II Study of Durvalumab (MEDI4736) (Anti-PD-L1 Antibody) in Combination With Tremelimumab (Anti-CTLA-4 Antibody) in Subjects With Advanced Rare Solid Tumors

This is an investigator initiated single institution, open-label study to evaluate the antitumor activity, safety, and tolerability of durvalumab in combination with tremelimumab in subjects with select advanced rare solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Rare Disease
• Intervention / Treatment: Drug: Durvalumab; Drug: Tremelimumab

Detailed Description

This is an investigator initiated single institution, open-label study to evaluate the antitumor activity, safety, and tolerability of durvalumab in combination with tremelimumab in subjects with select advanced rare solid tumors. The dose-exploration phase, conducted across a range of tumor types, has been completed. The dose-expansion phase is ongoing and includes certain soft tissue sarcomas, neuroendocrine tumors and thymic carcinoma. Therefore, subjects diagnosed with any of those rare tumors are excluded from this trial. Given the safety and tolerability data in the previous and ongoing studies (Study D4190C00010 and D4190C00006), the selected dose for evaluation in all subjects enrolled in this trial is as follows:

Durvalumab, 1500 mg Q4W (equivalent to 20 mg/kg Q4W) intravenously for 13 doses and Tremelimumab 300 mg intravenously as a single dose on cycle 1 day 1 only. Weight-based dosing should be utilized for patients <30 kg: durvalumab 20 mg/kg and tremelimumab 1 mg/kg. Tremelimumab will be administered first and the infusion duration will be approximately 1 hour. The durvalumab infusion will start approximately 1 hour after the end of the tremelimumab infusion and the infusion will be administered over approximately 1 hour.

The project Surveillance of Rare Cancers in Europe (RARECARE) collected data on cancers from 89 population-based cancer registries in 21 European countries, making it possible to study the epidemiology of these cancers as a whole in a large and heterogeneous population. Working from this database and the literature, a RARECARE working group produced a new list of cancers and developed a new definition of rare cancers (incidence < 6/100,000/year). This definition and working list are adopted for this rare tumor immunotherapy study.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Julie C Martin, DNP; Phone Number: 3667 864-455-3600; Email: julie.martin@prismahealth.org
• Study Contact Backup: Name: Jan Kueber, RN, BSN; Phone Number: 3774 864-455-3600; Email: jan.kueber@prismahealth.org

Study Locations

• United States
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Greenville Health System Cancer Institute
      • Contact: Fiona Davidson, RN, BSN; Phone Number: 3737 864-455-3600; Email: fiona.davidson@prismahealth.org
      • Contact: Lisa M Johnson, RN, BSN; Phone Number: 3735 8644553600; Email: lisa.johnson@prismahealth.org
      • Principal Investigator: W. Jeff Edenfield, MD
      • Sub-Investigator: Ki Y Chung, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of a rare advanced solid malignancy meeting EORTC criteria.
• Subjects must have failed or been ineligible to receive standard treatment options if available.
• Subjects must be amenable to biopsy of a tumor site or have recent (< 2 years) archival material available.
• ECOG performance status of 0 to 2.
• Life expectancy > 3 months.
• Adequate normal organ and marrow function including: hemoglobin > 9.0 g/dl; ANC > 1500 per mm3; platelet count > 100,000 per mm3; bilirubin < 1.5 x ULN; ALT/AST < 2.5 x ULN unless liver metastases present in which case must be < 5 x ULN; creatinine clearance > 40 ml/min by Cockcroft-Gault or 24 hour urine collection

Exclusion Criteria:

• Previous treatment with durvalumab or tremelimumab.
• Prior treatment with any checkpoint inhibitor (including anti-CTLA-4, anti-PD-1 and anti-PD-L1).
• Rare malignancies under investigation in other studies including thymic carcinoma, certain sarcomas, and neuroendocrine tumors.
• Untreated central nervous system metastatic disease.
• Active or documented autoimmune disease within previous 2 years.
• Uncontrolled psoriasis.
• Prior chemotherapy within 28 days of the first dose of durvalumab or tremelimumab.
• Steroid exposure within 28 days of the first dose of durvalumab or tremelimumab with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid

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: Single Arm; Durvalumab, 1500 mg Q4W (equivalent to 20 mg/kg Q4W) intravenously for 13 doses and Tremelimumab 300mg intravenously as a single dose on cycle 1 day 1 only.	Drug: Durvalumab; intravenous administration; Other Names: MEDI4736; Drug: Tremelimumab; intravenous administration; Other Names: CP-675,206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antitumor Activity	To evaluate the antitumor activity of durvalumab in combination with tremelimumab based on immune-related Response Evaluation Criteria	24 months
Incidence of Treatment-Emergent and Non Treatment-Emergent Adverse Events [Safety and Tolerability]	To assess the safety and tolerability of durvalumab in combination with tremelimumab	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of programmed cell death protein 1 (PD-1)	To evaluate the pharmacodynamic activity of durvalumab in combination with tremelimumab in the tumor microenvironment	24 months

Collaborators and Investigators

• Sponsor: Prisma Health-Upstate
• Collaborators: AstraZeneca; MedImmune LLC
• Investigators: Principal Investigator: William J Edenfield, MD, Prisma Health-Upstate

Publications and helpful links

General Publications

• Edenfield WJ, Chung K, O'Rourke M, Cull E, Martin J, Bowers H, Smith W, Gluck WL. A Phase II Study of Durvalumab in Combination with Tremelimumab in Patients with Rare Cancers. Oncologist. 2021 Sep;26(9):e1499-e1507. doi: 10.1002/onco.13798. Epub 2021 May 8.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 10, 2016
• First Submitted That Met QC Criteria: October 17, 2016
• First Posted (Estimated): October 19, 2016

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: cancer, malignancy
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Rare Diseases; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab
• Other Study ID Numbers: ESR-15-11633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: aggregate data only

Drug and device information, study documents

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