Clinical Trials /

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

NCT03811652

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.

Related Conditions:
  • Colorectal Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Prostate Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
MEDI7247NSCLC-Sq/HNSCC

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

NameTypeDescriptionInterventions
NSCLC-Sq/HNSCCExperimentalPatients 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.
  • MEDI7247
Small Cell Lung CancerExperimentalPatients with advanced SCLC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen.
  • MEDI7247
Colorectal CancerExperimentalPatients 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.
  • MEDI7247
Pancreatic Ductal AdenocarcinomaExperimentalPatients 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.
  • MEDI7247
Metastatic Castration-Resistant Prostate CancerExperimentalPatients with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.
  • MEDI7247
Other advanced/metastatic target expressing solid tumorsExperimentalPatients 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
  • MEDI7247

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:Recruiting
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

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