Clinical trial NCT03811652: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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)
Keywords: Medi7247
non small cell lung cancer
head and neck cancer
small cell lung cancer
colorectal cancer
prostate cancer
pancreatic adenocarcinoma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2019-01-22
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Occurrence of Adverse Events
timeFrame: From time of informed consent through 90 days post end of treatment
measure: Occurrence of Serious Adverse Events
timeFrame: From time of informed consent through 90 days post end of treatment
measure: Occurrence of Dose Limiting Toxicities
timeFrame: During the evaluation period of 21 days post first dose
measure: Number of patients with changes in laboratory parameters from baseline
timeFrame: From time of informed consent through 90 days post end of treatment
measure: Number of patients with changes in vital signs parameters from baseline
timeFrame: from time of informed consent through 21 days post last dose
measure: Number of patients with changes in electrocardiogram results from baseline
timeFrame: from time of informed consent through 21 days post last dose
measure: Percentage of patients with changes in laboratory parameters from baseline
timeFrame: from time of informed consent through 90 days post end of treatment
Secondary outcomes:
measure: MEDI7247 maximum observed concentration (Cmax)
timeFrame: From first dose through 90 days post end of treatment
measure: MEDI7247 terminal half life (t1/2)
timeFrame: From first dose through 90 days post end of treatment
measure: MEDI7247 area under the concentration/time curve (AUC)
timeFrame: from first dose through 90 days post end of treatment
measure: MEDI7247 clearance
timeFrame: from first dose through 90 days post end of treatment
measure: Number of subjects who develop anti-drug antibodies
timeFrame: first dose through 90 days post end of treatment
measure: Best Overall Response
timeFrame: From time of informed consent and up to 90 days post end of treatment
measure: Objective Response Rate (ORR)
timeFrame: From time of informed consent and up to 2 years after last subject in
measure: Time to Response (TTR)
timeFrame: From time of informed consent and up to 90 days post end of treatment
measure: Duration of Response (DoR)
timeFrame: From time of informed consent and up to 2 years after last subject in
measure: Progression Free Survival (PFS)
timeFrame: From time of informed consent and up to 2 years after last subject in
measure: Disease Control (DC)
timeFrame: From time of informed consent and up to 2 years after last subject in
measure: Overall Survival (OS)
timeFrame: From time of informed consent and up to 2 years after last subject in
Other outcomes:
Locations:
city: Huntersville
country: United States
facility: Research Site
state: North Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Toronto
country: Canada
facility: Research Site
state: Ontario
Study officials:
References: