A Phase 1, Open-label, Dose-escalation and Expansion Study of MEDI1191 Administered Intratumorally as Monotherapy and in Combination with Durvalumab in Subjects with Advanced Solid Tumors. Sub-study title: CD8+ Imaging Sub-study Protocol
- Conditions
- cancersubcutaneous/cutaneous lesions10027655
- Registration Number
- NL-OMON52188
- Lead Sponsor
- MedImmune, LLC, a wholly owned subsidiary of AstraZeneca PLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 14
Please note that due to removing inclusion/ exclusion criteria not relevant for
the protocol conducted in The Netherlands, the numbers deviate from those in
the Main Protocol.
Subjects must meet all of the following criteria:
1. Subjects >= 18 years of age.
2. Have given written informed consent prior to any study prior to performing
any protocol related procedures, including screening evaluations.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
4. Have at least 1 measurable lesion, other than the planned injected
lesion(s), using standard techniques by RECIST v1.1. Injected tumor lesion(s)
must be deemed clinically feasible for injection by the investigator.
a. A previously irradiated lesion, or a lesion subjected to other loco-regional
therapy, can be considered a target lesion only if the lesion has clearly
progressed during or after most recent therapy, and is well defined, measurable
per RECIST v1.1.
b. Subjects undergoing fresh tumor biopsies must have additional non-target
lesions that can be biopsied at acceptable risk as judged by the investigator
or if no other lesion is deemed suitable for biopsy, then a RECIST v1.1 target
lesion used for biopsy must be >= 2 cm in longest diameter.
5. Adequate bone marrow, renal, and hepatic function
a. Hematological (criteria listed cannot be met with recent blood transfusions
or require ongoing growth factor support within 2 weeks of starting study
treatment):
i. Absolute neutrophil count >= 1.5 × 109/L (1,500/mm3).
ii. Platelet count >= 100 × 109/L (100,000/mm3).
iii. Hemoglobin >= 9.0 g/dL within first 2 weeks prior to first dose.
b. Renal: calculated creatinine clearance (CrCL) (Cockcroft-Gault formula will
be used to calculate CrCL) or 24-hour urine CrCl > 50 mL/min.
c. Hepatic:
i. TBL <= 1.5 × ULN; for subjects with documented/suspected Gilbert's syndrome
or liver metastases, bilirubin <= 3 × ULN.
ii. AST and ALT <= 3 × ULN if no demonstrable liver metastasis; <= 5 x ULN in the
presence of liver metastases.
iii. Albumin > 3 g/dL.
iv. International normalized ratio (INR) and activated partial thromboplastin
time (aPTT) < 1.5 × ULN.
6. Prior to the first dose of MEDI1191, subjects with central nervous system
(CNS) metastases must have been treated and must be asymptomatic and meet the
following:
a. No concurrent treatment, inclusive of but not limited to surgery, radiation,
and/or corticosteroids.
b. Subjects must be clinically stable with no CNS symptoms following CNS
treatment for a period of at least 28 days prior to first dose of MEDI1191.
c. At least 7 days since last dose of corticosteroids first dose of MEDI1191.
NOTE: Subjects with clinical symptoms or cord compression or with
leptomeningeal disease are excluded from the study.
7. Cessation of immunosuppressive medications including systemic
corticosteroids at doses exceeding 12 mg/day prednisone or equivalent,
methotrexate, azathioprine, ustekinumab (Stelara®), and tumor necrosis factor
(TNF) a/IL 6 blockers for at least 7 days prior to the first dose of MEDI1191
(corticosteroids at doses of 12 mg/day prednisone equivalent or lower, inhaled,
intranasal, intraarticular, and topical steroids are permitted).
8. The imaging and the results of imaging done up to 6 months prior to
screening (ie, >= 1 additional time
Please note that due to removing inclusion/ exclusion criteria not relevant for
the protocol conducted in The Netherlands, the numbers deviate from those in
the Main Protocol.
Any of the following would exclude the subject from participation in the study:
1. Prior IL-12 either alone or as part of a treatment regimen.
2. Concurrent enrollment in another clinical study within 30 days prior to
treatment administration, unless it is an observational (non interventional)
clinical study or the follow-up period of an interventional study.
3. Receipt of live attenuated vaccines within 30 days prior to the first dose
of study treatment. Subjects who receive study treatment should not receive
live or live attenuated vaccine during the study and 30 days after the last
dose of investigational products.
4. Known allergy or hypersensitivity to any component of MEDI1191 or durvalumab
formulations.
5. Active or prior documented autoimmune disorders within the past 5 years
prior to the first scheduled dose of study treatment. The following are
exceptions to this criterion:
a. Subjects with vitiligo or alopecia.
b. Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement.
c. Any chronic skin condition that does not require systemic therapy.
d. Subjects with celiac disease controlled by diet alone.
6. History of primary immunodeficiency, other immune-deficiency states (eg,
myelodysplastic disorders, marrow failure states, human immunodeficiency virus
infection [even if viral load is undetectable], history of solid organ
transplant, bone marrow allograft), or active tuberculosis (in settings where
there is clinical or radiographic evidence of tuberculosis, active disease must
be excluded prior to enrollment in line with local practice).
7. History of coagulopathy resulting in uncontrolled bleeding, eg, hemophilia,
von Willebrand's disease. History of other bleeding disorders or a Grade >= 3
bleeding event within 3 months prior to first dose of investigational products.
8. Require continuous anticoagulation or antiplatelet therapy (except for <= 100
mg acetylsalicylic acid [ASA]) which cannot be interrupted for more than 7 days
for IT delivery of MEDI1191.
9. Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or
hormonal therapy for cancer. NOTE: Concurrent use of hormones for
noncancer-related conditions (eg, insulin for diabetes and hormone replacement
therapy for post-menopausal symptoms) or specific cancer-related conditions
(ie, LHRH-based hormonal therapy for prostate cancer with documented
progression) is acceptable. Local treatment of isolated lesions for palliative
intent is acceptable (eg, by local surgery or radiotherapy)
10. Receipt of any conventional or investigational anticancer therapy within 21
days or palliative radiotherapy within 7 days prior to the first dose of study
treatment. For subjects who have received prior immunotherapy, the following
additional exclusion criteria apply:
a. Received only one dose of prior immunotherapy agent alone or as part of a
combination regimen within 21 days.
b. Experienced a toxicity that led to permanent discontinuation of prior
immunotherapy
c. All AEs while receiving prior immunotherapy did not resolve to <= Grade 1 or
baseline prior to screening for this study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Sub-study, Biomarkers:<br /><br>• The amount and changes of 89Zr-Df-IAB22M2C uptake (CD8+ PET signal) using PET<br /><br>imaging at baseline and post-treatment in tumor lesions and reference normal<br /><br>tissues, as determined<br /><br>• The correlation of 89Zr-Df-IAB22M2C uptake (CD8+ PET signal) as determined by<br /><br>SUV-quantitative measures with CD8+ TIL density defined by IHC analysis of<br /><br>biopsied tumor tissue.<br /><br>• PET imaging signal level and changes from baseline to post-treatment with<br /><br>levels and changes in other exploratory biomarkers beyond CD8+ IHC (eg, TMB,<br /><br>NKp46, CD4+, PD-1, PD-L1 IHC, tumor transcriptomic changes, peripheral blood<br /><br>cytokines, and immune cell changes).<br /><br>• The amount and changes of 89Zr-Df-IAB22M2C uptake (CD8+ PET signal) using PET<br /><br>imaging at baseline and posttreatment with individual patient responses (CR,<br /><br>PR, SD and PD, iCR, iPR, iSD, and iPD) and lesion level changes.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Sub-study, Biomarkers:<br /><br>• The amount and changes of 89Zr-Df-IAB22M2C uptake (CD8+ PET signal) using PET<br /><br>imaging at baseline and post-treatment in tumor lesions and reference normal<br /><br>tissues, as determined<br /><br>• The correlation of 89Zr-Df-IAB22M2C uptake (CD8+ PET signal) as determined by<br /><br>SUV-quantitative measures with CD8+ TIL density defined by IHC analysis of<br /><br>biopsied tumor tissue.<br /><br>• PET imaging signal level and changes from baseline to post-treatment with<br /><br>levels and changes in other exploratory biomarkers beyond CD8+ IHC (eg, TMB,<br /><br>NKp46, CD4+, PD-1, PD-L1 IHC, tumor transcriptomic changes, peripheral blood<br /><br>cytokines, and immune cell changes).<br /><br>• The amount and changes of 89Zr-Df-IAB22M2C uptake (CD8+ PET signal) using PET<br /><br>imaging at baseline and post-treatment with individual patient responses (CR,<br /><br>PR, SD and PD, iCR, iPR, iSD, and iPD) and lesion level changes.</p><br>