Ph1 to Assess Safety, Tolerability of Tremelimumab/ Tremelimumab+MEDI4736 in Japanese Solid Malignancies/ Mesothelioma

A Ph1 Open-Label Multicentre Study to Assess Safety, Tolerability, PK and Anti-tumor Activity of Tremelimumab /Tremelimumab With MEDI4736 in Japanese With Advanced Solid Malignancies or Tremelimumab in Japanese With Malignant Mesothelioma

A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, PK and Preliminary Anti-tumor Activity when given as a monotherapy of Tremelimumab or Tremelimumab in combination with MEDI4736 in Japanese Patients with Advanced Solid Malignancies, and when given as a monotherapy of tremelimumab in Second- or Third-line Treatment of Japanese Subjects with Unresectable Pleural or Peritoneal Malignant Mesothelioma

Study Overview

• Status: Completed
• Conditions: Part A and B: Advanced Solid Malignancies; Part C: Malignant Mesothelioma
• Intervention / Treatment: Drug: Tremelimumab; Drug: MEDI4736

Detailed Description

Primary objectives Part A: To investigate the safety and tolerability of tremelimumab when given to Japanese patients with advanced solid malignancies and define the dose(s) for further clinical evaluation.

Part B: To investigate the safety and tolerability of tremelimumab in combination with MEDI4736 when given to Japanese patients with advanced solid malignancies and to define the dose(s) for further clinical evaluation.

Part C: To investigate the safety and tolerability of tremelimumab when given to Japanese patients with unresectable pleural or peritoneal malignant mesothelioma.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Bunkyo-ku, Japan, 113-8431
    • Research Site
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Hiroshima-shi, Japan, 734-8551
    • Research Site
  • Nagoya-shi, Japan, 464-8681
    • Research Site
  • Nishinomiya-shi, Japan, 663-8501
    • Research Site
  • Okayama-shi, Japan, 702-8055
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Research Site
  • Sapporo-shi, Japan, 003-0804
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Research Site
  • Ube-shi, Japan, 755-0241
    • Research Site
  • Yokohama-shi, Japan, 236-0051
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Part A and B:

Inclusion Criteria: 1. Japanese aged at least 20 years old at a time of enrollment. 2. Histological or cytological confirmation of a solid malignant tumor excluding lymphoma that is refractory to standard therapies or for which no standard therapies exist. 3. ECOG Performance Status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks at a time of randomization. 4. At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT, MRI or plain X-ray and is suitable for repeated assessment. 5. Adequate bone marrow, hepatic, and renal function 6. Willingness to provide consent for archival biopsy samples if available.

Exclusion Criteria: 1. Received any prior treatment with monoclonal antibody against Programmed death 1 (PD1), Programmed death ligand 1 (PD-L1) and CTLA-4 (eg, ipilimumab) 2. The last dose of prior chemotherapy or radiation therapy was received less than 2 weeks prior to randomization 3 Currently receiving systemic corticosteroids or other immunosuppressive medications or has a medical condition that requires the chronic use of corticosteroids. 4. Receipt of live attenuated vaccination within 30 days of starting tremelimumab treatment 5. Active, untreated central nervous system (CNS) metastasis (subjects with brain metastases who are identified at screening 6. History of other malignancy unless the subject has been disease-free for at least 3 years. 7. Any unresolved chronic toxicity CTCAE grade ≥2 from previous anticancer therapy at the time of randomization, 8. Major surgical procedure within 30 days of starting

Part C:

Inclusion Criteria: 1. Japanese aged 20 and over at the time of consent 2. Histologically and/or cytologically confirmed pleural or peritoneal malignant mesothelioma 3. Disease not amenable to curative surgery 4. ECOG Performance status 0-1 5. Progressed after previous receipt of 1-2 prior systemic treatments for advanced disease that included a first-line pemetrexed (or anti-folate)-based regimen in combination with platinum agent. 6. Measurable disease, defined as at least 1 lesion (measurable) that can be accurately assessed at baseline by computed tomography CT or MRI and is suitable for repeated assessment. 7. Adequate bone marrow, hepatic, and renal function Exclusion Criteria: 1. Subjects who failed more than 2 prior systemic treatment regimens for advanced malignant mesothelioma 2. Received any prior mAb against CTLA-4, PD1 or PD-L1 3. History of chronic inflammatory or autoimmune disease. 4. Symptomatic, untreated CNS metastasis. 5. Any serious uncontrolled medical disorder or active infection that would impair the subject's ability to receive investigational product. 6. History of other malignancy. 7. History of diverticulitis, inflammatory bowel disease, sarcoidosis syndrome 8. Currently receiving systemic corticosteroids or other immunosuppressive medications. 9. Vaccinated with live attenuated vaccines within 30 days prior to starting tremelimumab treatment 10. Not recovered from all toxicities associated with prior cancer treatment to acceptable baseline status, or a NCI CTCAE ver.3.0 Grade of 0 or 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Part A; Dose escalation of tremelimumab mono therapy for advanced solid malignancies	Drug: Tremelimumab; Tremelimumab administered intravenously
Other: Part B; Combination therapy of tremelimumab and MEDI4736 for advanced solid malignancies	Drug: Tremelimumab; Tremelimumab administered intravenously; Drug: MEDI4736; MEDI4736 administered intravenously.
Other: Part C; Fixed dose of tremelimumab for malignant mesothelioma	Drug: Tremelimumab; Tremelimumab administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event	To investigate the safety and tolerability of tremelimumab and/ or MEDI4736 when given to Japanese patients	From time of informed consent to 90 days after the last dose

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Fujiwara Y, Takahashi Y, Okada M, Kishimoto T, Kondo S, Fujikawa K, Hayama M, Sugeno M, Ueda S, Komuro K, Lanasa M, Nakano T. Phase I Study of Tremelimumab Monotherapy or in Combination With Durvalumab in Japanese Patients With Advanced Solid Tumors or Malignant Mesothelioma. Oncologist. 2022 Sep 2;27(9):e703-e722. doi: 10.1093/oncolo/oyac099.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2014
• Primary Completion (Actual): January 27, 2017
• Study Completion (Actual): January 27, 2017

Study Registration Dates

• First Submitted: May 14, 2014
• First Submitted That Met QC Criteria: May 16, 2014
• First Posted (Estimate): May 19, 2014

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: December 11, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Neoplasms; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab
• Other Study ID Numbers: D4880C00010