A Study of MEDI9197 in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors

NCT02556463 | Terminated Phase 1

• 1 other identifier: D6410C00001
• Study Type: interventional
• Target: 53
• Locations: 3 countries
• Sites: 10

Brief Summary

To evaluate MEDI9197 when administered by intratumoral injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors.

Conditions

Solid Tumors; CTCL; Cancer

Keywords

MEDI9197; TLR 7/8 Agonist; Durvalumab; MEDI4736; Imfinzi

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with solid tumor cancers

  The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.

  From time of informed consent through 4 weeks after last dose of investigational product

• Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with CTCL

  The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.

  From time of informed consent through 6 months after last dose of investigational product

• Safety & tolerability as determined by dose limiting toxicities and maximum tolerated or assessed dose of MEDI9197 administered by IT injection in combo with durvalumab and durvalumab plus palliative radiation to subjects with solid tumor cancers.

  The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.

  From time of informed consent through 90 days after last dose of investigational product

Secondary Outcomes (11)

• The maximum concentration of MEDI9197 after the first injection

  Pre-dose to 24 hours post first dose

• The apparent terminal half-life of MEDI9197

  Pre-dose to 24 hours post first dose

• Percent change from baseline in cluster of differentiation 8 tumor infiltrating lymphocytes in tumor tissue

  Baseline to Day 50

• Percent change from baseline in serum inflammatory cytokine levels

  Pre-dose to end of study, up to 24 months

• Percent change from baseline in tumor measurements

  Pre-dose to disease progression, up to 12 months

Study Arms (4)

Escalation MEDI9197

EXPERIMENTAL

MEDI9197

Drug: MEDI9197

Escalation MEDI9197 with durvalumab

EXPERIMENTAL

MEDI9197 in combination with durvalumab

Drug: MEDI9197; Biological: durvalumab

Escalation MEDI9197 durvalumab radiation

EXPERIMENTAL

MEDI9197 in combination with durvalumab and palliative radiation

Drug: MEDI9197; Biological: durvalumab

MEDI9197 with palliative radiation

EXPERIMENTAL

MEDI9197 in combination with palliative radiation

Drug: MEDI9197

Interventions

MEDI9197 DRUG

Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)

Escalation MEDI9197; Escalation MEDI9197 durvalumab radiation; Escalation MEDI9197 with durvalumab; MEDI9197 with palliative radiation

durvalumab BIOLOGICAL

Subjects will receive durvalumab every 4 weeks

Also known as: MEDI4736

Escalation MEDI9197 durvalumab radiation; Escalation MEDI9197 with durvalumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and any locally required authorizations.
• Male and female subjects at least 18 years at the time of screening.
• Adequate organ function within 14 days of enrollment confirmed by laboratory results.
• Systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent.
• ECOG 0 or 1.
• Highly effective method of contraception from the date of the screening pregnancy test, and continued precautions for 6 months after the final dose of investigational product.
• Baseline Child-Pugh Score of A1 to B7.
• Life expectancy ≥ 12 weeks, as estimated by Royal Marsden Hospital Score of 0 or 1 at baseline.
• Subjects with hepatocellular carcinoma (HCC) are eligible if the tumor is defined as nodular type 1 or 2 only.
• Metastatic/locally advanced solid tumor malignancy that has progressed on, is refractory to, or for which there is no standard of care therapy.
• For subjects with cutaneous/subcutaneous lesions, subjects must have more than one measurable target lesion, at baseline, with a minimum of one lesion that meets protocol specified criteria.
• For subjects with deep-seated lesions, subjects must have more than one measurable target lesion at baseline (RECIST v1.1), with a minimum of one deep-seated lesion suitable for image-guided injection and that meets protocol specified criteria.
• Clinical diagnosis of CTCL, including documentation of a skin biopsy with histological findings consistent with CTCL or unconfirmed diagnosis of CTCL with confirmation biopsy at screening.
• Stage IB, IIA, or IIB disease: T1, T2 or T3 (patches, plaques or tumors) with measurable lesions.
• Previous treatment with at least one standard therapy used to treat the stage of disease at study entry; Stage IB, IIA or IIB CTCL.

You may not qualify if:

• Any of the following would exclude the subject from participation in the study:
• Subjects who have received prior immunotherapy \[(including but not limited to CTLA-4, oncolytic virus, oncolytic peptide-all require 100 day washout), programmed death ligand (PDL)-1, or programmed cell death 1 antagonists-both require 14 day washout)\] are NOT permitted to enroll, with protocol exceptions.
• Pregnant or lactating.
• Active bacterial, fungal, or viral infections, including chronic or active hepatitis B, chronic or active hepatitis C, or active hepatitis A. Prior documented infections must have resolved.
• Active or prior documented autoimmune or inflammatory disorders, with exceptions per protocol. Includes known allergy to sesame oil and/or nuts.
• Immune-deficiency states - myelodysplastic disorders, marrow failures, human immunodeficiency virus (HIV) infection, history of solid organ transplant or bone marrow allograft, or recent pregnancy.
• Requires continuous (daily) anticoagulation or antiplatelet therapy (including anti aggregants), acetylsalicylic acid (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs).
• History of coagulopathy resulting in uncontrolled bleeding or other bleeding disorders.
• Rapidly progressing disease per protocol.
• Untreated or uncontrolled central nervous system (CNS) involvement.
• Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment; with exceptions per protocol.
• Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1, with exception of alopecia, vitiligo.
• Uncontrolled concurrent illness.
• Major surgery within 4 weeks prior to study entry or still recovering from prior surgery.
• Receipt of live, attenuated vaccine within 28 days prior to study entry.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (10)

Research Site

San Francisco, California, 94115, United States

Location

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Minneapolis, Minnesota, 55455, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

New York, New York, 10029, United States

Location

Research Site

Chapel Hill, North Carolina, 27599-7305, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Toronto, Ontario, M5G 1Z6, Canada

Location

Research Site

Villejuif, 94805, France

Location

Related Publications (1)

• Siu L, Brody J, Gupta S, Marabelle A, Jimeno A, Munster P, Grilley-Olson J, Rook AH, Hollebecque A, Wong RKS, Welsh JW, Wu Y, Morehouse C, Hamid O, Walcott F, Cooper ZA, Kumar R, Ferte C, Hong DS. Safety and clinical activity of intratumoral MEDI9197 alone and in combination with durvalumab and/or palliative radiation therapy in patients with advanced solid tumors. J Immunother Cancer. 2020 Oct;8(2):e001095. doi: 10.1136/jitc-2020-001095.

  PMID: 33037117 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

MEDI9197; durvalumab

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 22, 2015
• Study Start: November 4, 2015
• Primary Completion: October 26, 2018
• Study Completion: October 26, 2018
• Last Updated: December 19, 2018

Record last verified: 2018-12

Locations

US (8); CA (1); FR (1)