A Phase 1, 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
- Conditions
- Part A and B: Advanced Solid Malignancies, Part C: Malignant Mesothelioma
- Registration Number
- JPRN-jRCT2080222502
- Lead Sponsor
- AstraZeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Sex
- All
- Target Recruitment
- Not specified
Part A and B:
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.
Part C:
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
Part A and B:
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 or more from previous anticancer therapy at the time of randomization
8. Major surgical procedure within 30 days of starting tremelimumab
Part C
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 Grade of 0 or 1
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method