A Phase 1 Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination with Tremelimumab (Anti-CTLA-4 Antibody) in Subjects with Advanced Solid Tumors
- Conditions
- Gevorderde solide tumorenAdvanced Solid Tumors
- Registration Number
- NL-OMON47386
- Lead Sponsor
- MedImmune, LLC, a wholly owned subsidiary of AstraZeneca PLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
Subjects must meet all of the following criteria:
1. Male and female subjects; age >= 18 years at the time of study entry.
2. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations.
3. Subjects must have histologic documentation of UBC, SCLC, STS, TNBC, HPV-positive anogenital cancer (anal, cervical, and vaginal), MSI-H CRC, or high-grade epithelial ovarian cancer (including fallopian tubal carcinoma and peritoneal carcinoma).
4. Under Protocol Amendment 3 and beyond, subjects with UBC must meet the following criteria in addition to those for the overall study population:
a. Subjects must have histologically or cytologically confirmed inoperable or metastatic transitional cell (including transitional cell and mixed transitional cell/non-transitional cell histologies) carcinoma of the urothelium (including the urinary bladder, ureter, urethra, and renal pelvis).
b. Subjects must have received and have progressed or are refractory to at least 1 but not more than 2 prior lines of systemic therapy for inoperable or metastatic disease, including a standard platinum-based regimen. Interval progression between 2 lines of therapy defines separate lines of therapy. Prior definitive chemoradiation for locally advanced disease, adjuvant treatment, or neoadjuvant treatment will be considered a prior line of therapy, provided that progression has occurred < 12 months from therapy [for chemoradiation and adjuvant treatment] or < 12 months from surgery [for neoadjuvant treatment].
c. Subjects must have documented radiographic disease progression as assessed by the investigator at the time of study entry.
d. Subjects with UBC must consent to provide an archived tumor specimen from within 6 months prior to study entry (ie, from subject signing consent to participate in the study) for PD-L1 IHC analysis. If not available, subjects must have at least 1 lesion amenable to biopsy and consent to provide a pre-treatment fresh biopsy. Tumor lesions used for biopsy should not be lesions used as RECIST target lesions. Tumor tissue for PD-L1 analysis must be shipped to, and confirmed as received by the Sponsor or designated central vendor prior to the first dose of investigational product. However, subjects may be dosed before PD-L1 results are known. It is highly recommended that efforts are taken to confirm the presence of tumor cells within the tumor sample prior to shipping for PD-L1 analysis. Additional archival tumor tissue, regardless of age, is also required, if available, to support exploratory analyses. On treatment and end of treatment biopsies are optional for UBC subjects. PD-L1 status determined by IHC testing from tumor samples evaluated for screening into Study CD ON MEDI4736 1108 may be used if derived from a sample taken <= 6 months prior to study entry.
e. After enrollment of approximately 77 UBC subjects (and a minimum of 30 PD-L1 negative UBC subjects) under Protocol Amendment 3 and beyond, further enrollment may be restricted to PD-L1 negative subjects only as described in Section 3.1.1. If enrollment is restricted to PD-L1 negative subjects only, subjects must have known PD-L1 status prior to treatment with MEDI4736 and tremelimumab.
f. Sub
Any of the following would exclude the subject from participation in the study:
1. Prior participation in clinical studies that include MEDI4736 alone or in combination with other agents, where the study has registrational intent and the analyses for the primary endpoint have not yet been completed.
2. History of severe allergic reactions (ie, Grade 4 allergy, anaphylactic reaction from which the subject did not recover within 6 hours of institution of supportive care) to any unknown allergens or any components of the study drug formulations.
3. Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener syndrome) within the past 2 years. Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave*s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
4. Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression. Subjects with previously treated central nervous system metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management for at least 14 days prior to first dose of MEDI4736 and tremelimumab are permitted to enroll.
5. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
6. Receipt of any conventional or investigational anticancer therapy not otherwise specified above within 28 days prior to the first dose of MEDI4736 and tremelimumab.
7. Any concurrent chemotherapy, IMT, or biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. In addition, local treatment (eg, by local surgery or radiotherapy) of isolated lesions for palliative intent is acceptable beyond the DLT evaluation period with prior consultation and in agreement with the medical monitor.
8. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1 with the exception of alopecia and laboratory values listed per the inclusion criteria. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by any of the investigational products may be included (eg, hearing loss) after consultation with the medical monitor.
9. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI4736 or tremelimumab. The following are exceptions to this criterion:
a. Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection).
b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent.
c. Steroids as premedication for hypersensitivity reactions (eg, computedtomography [CT] scan premedication).
10. History of primary immunodeficiency, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
11. Known positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or C or active hepatitis A.
12. Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products (NOTE: Subjects, if enrolled, should not receive live vaccine during the study and 180 days after the last dose o
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>The primary safety endpoint as assessed by the presence of adverse events<br /><br>(AEs), serious adverse events (SAEs), DLTs, and changes from baseline in<br /><br>laboratory parameters, physical examinations, electrocardiograms, and vital<br /><br>signs.<br /><br>The primary efficacy endpoint in subjects with PD-L1 negative UBC is objective<br /><br>response (OR) based on RECIST v1.1 as determined by the investigator.</p><br>
- Secondary Outcome Measures
Name Time Method