A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors

Metastatic Castration-resistant Prostate Cancer (mCRPC) Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03811652
• Other study ID #: D8540C00002
• Status: Completed
• Phase: Phase 1
• Start date: December 20, 2018
• Est. completion date: December 10, 2019

Study information

• Verified date: December 2019
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 10, 2019
• Est. primary completion date: December 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer (CRC)
• Colorectal Neoplasms
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Lung Neoplasms
• Metastatic Castration-resistant Prostate Cancer (mCRPC)
• Non Small Cell Lung Cancer Squamous (NSCLC-Sq)
• Pancreatic Ductal Adenocarcinoma (PDAC)
• Prostatic Neoplasms
• Small Cell Lung Cancer (SCLC)
• Small Cell Lung Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• MEDI7247
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule

Locations

Country	Name	City	State
Canada	Research Site	Toronto	Ontario
United States	Research Site	Huntersville	North Carolina
United States	Research Site	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of Adverse Events	To assess the occurrence of adverse events	From time of informed consent through 90 days post end of treatment
Primary	Occurrence of Serious Adverse Events	To assess the occurrence of serious adverse events	From time of informed consent through 90 days post end of treatment
Primary	Occurrence of Dose Limiting Toxicities	To assess the occurrence of toxicities and abnormal laboratory results that may limit further dose administration	During the evaluation period of 21 days post first dose
Primary	Number of patients with changes in laboratory parameters from baseline	To assess serum chemistry, hematology, urinalysis and coagulation parameters	From time of informed consent through 90 days post end of treatment
Primary	Number of patients with changes in vital signs parameters from baseline	to assess changes in vital signs	from time of informed consent through 21 days post last dose
Primary	Number of patients with changes in electrocardiogram results from baseline	to assess changes in ECG	from time of informed consent through 21 days post last dose
Primary	Percentage of patients with changes in laboratory parameters from baseline	to assess changes in serum chemistry, hematology, urinalysis, and coagulation parameters	from time of informed consent through 90 days post end of treatment
Secondary	MEDI7247 maximum observed concentration (Cmax)	To characterize MEDI7247 single agent Pharmacokinetics	From first dose through 90 days post end of treatment
Secondary	MEDI7247 terminal half life (t1/2)	To characterize single agent MEDI7247 pharmacokinetics	From first dose through 90 days post end of treatment
Secondary	MEDI7247 area under the concentration/time curve (AUC)	To characterize single agent MEDI7247 pharmacokinetics	from first dose through 90 days post end of treatment
Secondary	MEDI7247 clearance	to characterize the single agent MEDI7247 pharmacokinetics	from first dose through 90 days post end of treatment
Secondary	Number of subjects who develop anti-drug antibodies	To characterize MEDI7247 immunogenicity	first dose through 90 days post end of treatment
Secondary	Best Overall Response	To assess antitumor activity of MEDI7247	From time of informed consent and up to 90 days post end of treatment
Secondary	Objective Response Rate (ORR)	To assess antitumor activity of MEDI7247	From time of informed consent and up to 2 years after last subject in
Secondary	Time to Response (TTR)	To assess antitumor activity of MEDI7247	From time of informed consent and up to 90 days post end of treatment
Secondary	Duration of Response (DoR)	To assess antitumor activity of MEDI7247	From time of informed consent and up to 2 years after last subject in
Secondary	Progression Free Survival (PFS)	To assess the antitumor activity of MEDI7247	From time of informed consent and up to 2 years after last subject in
Secondary	Disease Control (DC)	To assess antitumor activity of MEDI7247	From time of informed consent and up to 2 years after last subject in
Secondary	Overall Survival (OS)	To assess antitumor activity of MEDI7247	From time of informed consent and up to 2 years after last subject in