Description:
To assess safety and tolerability, describe the dose-limiting toxicities, assess the
preliminary antitumor activity, determine the maximum tolerated dose (MTD) or the highest
protocol-defined dose (maximum administered dose) in the absence of establishing the MTD, and
a recommended dose for further evaluation of MEDI7247 in patients with selected advanced or
metastatic solid tumor malignancies that have received at least 1 prior line of treatment.
Title
- Brief Title: A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors
- Official Title: A Phase 1/1b Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI7247 in Patients With Advanced or Metastatic Disease in Selected Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
D8540C00002
- NCT ID:
NCT03811652
Conditions
- Non Small Cell Lung Cancer Squamous (NSCLC-Sq)
- Head and Neck Squamous Cell Carcinoma (HNSCC)
- Small Cell Lung Cancer (SCLC)
- Pancreatic Ductal Adenocarcinoma (PDAC)
- Colorectal Cancer (CRC)
- Metastatic Castration-resistant Prostate Cancer (mCRPC)
Interventions
Drug | Synonyms | Arms |
---|
MEDI7247 | | Colorectal Cancer |
Purpose
To assess safety and tolerability, describe the dose-limiting toxicities, assess the
preliminary antitumor activity, determine the maximum tolerated dose (MTD) or the highest
protocol-defined dose (maximum administered dose) in the absence of establishing the MTD, and
a recommended dose for further evaluation of MEDI7247 in patients with selected advanced or
metastatic solid tumor malignancies that have received at least 1 prior line of treatment.
Trial Arms
Name | Type | Description | Interventions |
---|
NSCLC-Sq/HNSCC | Experimental | Patients with advanced or metastatic NSCLC-Sq or HNSCC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen (platinum-based for HNSCC). PDL-1 positive patients should have received previous PD-1 or PD-L1 inhibitor where available. | |
Small Cell Lung Cancer | Experimental | Patients with advanced SCLC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen. | |
Colorectal Cancer | Experimental | Patients with metastatic adenocarcinoma of the colon or rectum who have received and have progressed, or have documented intolerance, on prior thymidylate synthase inhibitor (eg, 5-fluorouracil (5-FU), capecitabine, raltitrexed, tegafur-uracil (UFT), irinotecan, and oxaliplatin for metastatic disease. If patients progress within 6 months of their last dose of adjuvant therapy this should be considered as a line of therapy in the metastatic setting. Patients with known RAS wildtype tumors must have received and progressed, or have documented intolerance, on anti-EGFR antibody. Patients with microsatellite instability-high or deficient mismatch repair tumors, must have received and progressed, or have documented intolerance on a PD-1 inhibitor, or PD-1 inhibitor plus cytotoxic T-lymphocyte antigen-4 inhibitor treatment where available. | |
Pancreatic Ductal Adenocarcinoma | Experimental | Patients with unresectable, locally advanced or metastatic PDAC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior line of treatment. | |
Metastatic Castration-Resistant Prostate Cancer | Experimental | Patients with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting. | |
Other advanced/metastatic target expressing solid tumors | Experimental | Patients with advanced or metastatic solid tumors not defined by other treatment arms who have positive expression of the protein target and have exhausted all approved therapies | |
Eligibility Criteria
Inclusion Criteria:
1. Confirmed diagnosis of advanced or metastatic select solid tumors and either
progression on or documented intolerance to standard therapies
2. Age ≥ 18 years at the time of screening.
3. Written informed consent and any locally required authorization
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. At least 1 measurable target lesion by CT or MRI per RECIST Version 1.1 (excluding
mCRPC)
6. Adequate Liver Function: Aspartate Aminotransferase (AST) and Alanine Aminotransferase
(ALT) ≤ 2.5 × ULN (upper limit normal), Albumin > 3 g/dL, and serum total bilirubin
(TBL) ≤ 1.5 × ULN; (unless bilirubin rise is due to Gilbert's syndrome, hepatic
metastases or of non-hepatic origin, in which case TBL ≤ 3 × ULN is allowed)
7. Creatinine Clearance (CrCL) ≥ 40 mL/min
8. Adequate Hematopoesis: Absolute Neutrophil Count (ANC) ≥ 1,500/μL, Platelets ≥
100,000/μL, and Hgb ≥ 9 g/dL unassisted by transfusion or growth factor within 14 days
of screening
9. Provision of archival or fresh tumor tissue at screening
10. Female patients of childbearing potential who are sexually active with a nonsterilized
male partner must use at least one highly effective method of contraception, and must
agree to continue using such precautions for 90 days after the last dose of
investigational product.
11. Nonsterilized male patients who are sexually active with a female partner of
childbearing potential must use a male condom plus spermicide from 7 days
post-screening and for 90 days after receipt of the last dose of investigational
product.
Exclusion Criteria:
1. Active central nervous system (CNS) metastases, unless adequately treated and patients
have neurologically returned to baseline (except for residual signs or symptoms
related to the CNS treatment) and prednisolone 10 mg or less for more than 2 weeks
prior to enrollment. For SCLC, a brain MRI scan that was conducted ≤ 28 days from Day
1 is required.
2. Residual toxicity from prior anticancer therapy not resolved to NCI CTCAE v4.03 Grade
1, with the exception of alopecia/vitiligo at the time of first dose of
investigational product. For patients previously receiving immunotherapy, toxicities
that are unlikely to recover to Grade 1.
3. Royal Marsden Hospital (RMH) prognostic score 2 and 3 at baseline.
4. Treatment with anticancer therapy including chemotherapy, radiation therapy,
immunotherapy, biologic, or any investigational therapy within 21 days, or prior
palliative radiotherapy within 2 weeks of the first dose of investigational product.
5 Prior treatment with other Pyrrolobenzodiazepine-Antibody Drug Conjugates.
6 History of previous malignancies (except for locally curable cancers) unless a complete
remission was achieved at least 3 years prior to study entry AND no additional therapy is
required during the study period (except adjuvant hormonal therapy and bisphosphonate).
7. Failure to recover from major surgery or significant traumatic injury within 21 days of
first dose of study treatment.
8 History of hepatic sinusoidal obstruction syndrome, also called veno-occlusive disease 9.
History of capillary leak syndrome. 10 Blood transfusion within 14 days of study entry
except when needed for disease related anemia.
11. New York Heart Association classes III-IV congestive heart failure or serious cardiac
arrhythmia requiring treatment, history of myocardial infarction, unstable angina, vascular
stent, or coronary artery bypass graft within 6 months of the first dose of investigational
product. 12. Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
hepatitis C virus (HCV) infections at the time of screening.
13. Current severe active systemic disease including active concurrent malignancy 14.
Pregnancy and/or breastfeeding at time of screening 15. Concurrent enrollment in anther
clinical study involving an investigational treatment that is not an extension of another
MedImmune study with the same investigational product.
Maximum Eligible Age: | 101 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Occurrence of Adverse Events |
Time Frame: | From time of informed consent through 90 days post end of treatment |
Safety Issue: | |
Description: | To assess the occurrence of adverse events |
Secondary Outcome Measures
Measure: | MEDI7247 maximum observed concentration (Cmax) |
Time Frame: | From first dose through 90 days post end of treatment |
Safety Issue: | |
Description: | To characterize MEDI7247 single agent Pharmacokinetics |
Measure: | MEDI7247 terminal half life (t1/2) |
Time Frame: | From first dose through 90 days post end of treatment |
Safety Issue: | |
Description: | To characterize single agent MEDI7247 pharmacokinetics |
Measure: | MEDI7247 area under the concentration/time curve (AUC) |
Time Frame: | from first dose through 90 days post end of treatment |
Safety Issue: | |
Description: | To characterize single agent MEDI7247 pharmacokinetics |
Measure: | MEDI7247 clearance |
Time Frame: | from first dose through 90 days post end of treatment |
Safety Issue: | |
Description: | to characterize the single agent MEDI7247 pharmacokinetics |
Measure: | Number of subjects who develop anti-drug antibodies |
Time Frame: | first dose through 90 days post end of treatment |
Safety Issue: | |
Description: | To characterize MEDI7247 immunogenicity |
Measure: | Best Overall Response |
Time Frame: | From time of informed consent and up to 90 days post end of treatment |
Safety Issue: | |
Description: | To assess antitumor activity of MEDI7247 |
Measure: | Objective Response Rate (ORR) |
Time Frame: | From time of informed consent and up to 2 years after last subject in |
Safety Issue: | |
Description: | To assess antitumor activity of MEDI7247 |
Measure: | Time to Response (TTR) |
Time Frame: | From time of informed consent and up to 90 days post end of treatment |
Safety Issue: | |
Description: | To assess antitumor activity of MEDI7247 |
Measure: | Duration of Response (DoR) |
Time Frame: | From time of informed consent and up to 2 years after last subject in |
Safety Issue: | |
Description: | To assess antitumor activity of MEDI7247 |
Measure: | Progression Free Survival (PFS) |
Time Frame: | From time of informed consent and up to 2 years after last subject in |
Safety Issue: | |
Description: | To assess the antitumor activity of MEDI7247 |
Measure: | Disease Control (DC) |
Time Frame: | From time of informed consent and up to 2 years after last subject in |
Safety Issue: | |
Description: | To assess antitumor activity of MEDI7247 |
Measure: | Overall Survival (OS) |
Time Frame: | From time of informed consent and up to 2 years after last subject in |
Safety Issue: | |
Description: | To assess antitumor activity of MEDI7247 |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | MedImmune LLC |
Trial Keywords
- Medi7247
- non small cell lung cancer
- head and neck cancer
- small cell lung cancer
- colorectal cancer
- prostate cancer
- pancreatic adenocarcinoma
Last Updated
December 30, 2019