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Dose Escalation and Cohort Expansion of Safety and Tolerability Study of Intratumoral rAd.CD40L (ISF35) in Combination of Systemic Pembrolizumab in Patients With Refractory Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02719015
Recruitment Status : Withdrawn (No IND Serial #)
First Posted : March 24, 2016
Last Update Posted : November 24, 2017
Memgen, LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerated dose of rAd.CD40L (also called ISF35) when given with pembrolizumab to patients with melanoma. Researchers also want to learn if the highest tolerated dose of ISF35 and pembrolizumab can help to control the disease.

The safety of this drug combination will be also be studied.

Condition or disease Intervention/treatment Phase
Melanoma Drug: rAd.CD40L Drug: Pembrolizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Dose Escalation and Cohort Expansion of Safety and Tolerability Study of Intratumoral rAd.CD40L (ISF35) in Combination of Systemic Pembrolizumab in Patients With Refractory Metastatic Melanoma
Estimated Study Start Date : March 2018
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: rAd.CD40L + Pembrolizumab

The dose escalation phase will include rAd.CD40L dose escalation and increase in the number of injected sites/lesions. Once patients tolerate dose level 1 (1 injection site and 1x1011vp-MTD) in Dose Escalation cohort, Expansion cohort will open with same maximum number of injection sites at maximum tolerated dose from Dose Escalation cohort.

All participants receive same dosage of Pembrolizumab in both phases.

Drug: rAd.CD40L

Dose Escalation Phase Starting Dose: 5x10^10 vp per tumor as an injection directly into 1-3 tumors every 3 weeks. Same tumors injected for each of the 4 injections at week 0, 3, 6 and 9. If the dose well tolerated, the rAd.CD40L escalated to 1x10^11 vp. Subsequently enrolled patients injected at the same dose of 1x10^11 vp. Number of injected sites/tumors increased to two sites/lesions if patients have >/=2 injectable lesions, at the same injection dose of 1x10^10 up to three separate sites/lesions if patients have > 3 injectable lesions.

Dose Expansion Phase Starting Dose: MTD from Dose Escalation Phase.

Other Name: ISF35

Drug: Pembrolizumab
Dose Escalation and Expansion Phases: 2 mg/kg by vein every 3 weeks.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Intratumoral rAd.CD40L [ Time Frame: 3 weeks ]
    MTD defined as the dose with the smallest absolute difference between the estimate of pi and the true pT for which Prob (pi > pT | data) is less than 5%.

  2. Overall Response Rate (ORR) of Intratumoral rAd.CD40L [ Time Frame: 12 weeks ]
    Tumor response to therapy assessed using immune-related response criteria (irRC), which is a modified version of the World Health Organization (WHO) criteria.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Dose escalation: Patients with metastatic melanoma with measurable, stage III (in transit lesions) or stage IVA, IVB or IVC disease (at least 2 measurable lesions/tumors. Patients will be required to have one more lesion present than the number the current dose level requires since one lesion will be left untreated.
  2. Expansion cohorts: Patients with metastatic melanoma with measurable, stage III (in transit lesions) or stage IVA, IVB or IVC disease at least two measurable lesions/tumors
  3. Patients who have tested positive for a BRAF mutation may have received prior BRAF inhibitor therapy as a prior line of systemic therapy. Patients may have received up to 2 prior lines of therapy with a checkpoint inhibitor (CPI), which may have included pembrolizumab, nivolumab, or ipilimumab. These agents may have been administered as single-agent treatment, in combination with each other, or in combination with other agents. Patients who have received prior treatment with ipilimumab must have relapsed after achieving a response to prior ipilimumab treatment. This response may have been achieved with ipilimumab administered as single-agent therapy or in combination with another treatment. Patients who have received prior treatment with pembrolizumab or nivolumab must have progression of disease after at least 4 doses of either drug alone or in combination with other agents.
  4. Age >/= 18 years
  5. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 - 1 within 30 days of signing informed consent.
  6. Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
  7. Platelet count greater than or equal to 100,000/mm3
  8. white blood cell count (WBC) >/=3000/mm3
  9. Serum ALT and AST <3 the upper limit of normal (ULN); <5 ULN if there is liver involvement secondary to the tumor
  10. Serum creatinine </= 2.0 mg/dl
  11. Seronegative for HIV antibody
  12. Patients with a negative pregnancy test (urine or serum) must be documented within 14 days of screening for women of childbearing potential (WOCBP). A WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e. who has not had menses at any time in the preceding 12 consecutive months).
  13. Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, intrauterine device (IUD), or sponge plus spermicide. Abstinence is an acceptable form of birth control.

Exclusion Criteria:

  1. Patients who have previously received anti cluster of designation antigen 40 (CD40) (Agonistic) therapy prior Adjuvant Interferon (IFN-α), is allowed if last dose was received at least 6 months from enrolling to protocol.
  2. Active autoimmune disease requiring disease modifying therapy.
  3. Concurrent systemic steroid therapy higher than physiologic dose (>7.5 mg/Day of prednisone).
  4. Any form of active primary or secondary immunodeficiency.
  5. Prior malignancy except the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
  6. Subjects who have received prior oncolytic therapy or prior therapy with and TLR agonist including topical agents. Subjects that have received experimental vaccines or other immune therapies should be discussed with the medical monitor or the Principal Investigator (PI) to confirm eligibility.
  7. Active systemic infections requiring intravenous antibiotics.
  8. Prior systemic therapy, radiation therapy, or surgery within 28 days of starting study treatment. Palliative radiotherapy to a limited field or palliative cryoablation is allowed after consultation with the principle Investigator, at any time during the study participation including screening.
  9. Patients who are pregnant or nursing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02719015

Sponsors and Collaborators
M.D. Anderson Cancer Center
Memgen, LLC
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Principal Investigator: Adi Diab, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT02719015    
Other Study ID Numbers: 2015-0199
First Posted: March 24, 2016    Key Record Dates
Last Update Posted: November 24, 2017
Last Verified: November 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Refractory Metastatic Melanoma
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Antineoplastic Agents