Programmed Cell Death 1 + Selected Cell Therapy With Durvalumab (MEDI4736) and Tremelimumab in Metastatic Melanoma

NCT04223648 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: 2000025925
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this pilot study is to assess the feasibility of mobilizing PD-1+ T cells to the peripheral blood after a single treatment with tremelimumab/durvalumab in patients with treatment naïve metastatic melanoma.

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (1)

• PD1+ cell pharmacodynamic response in blood to tremelimumab/durvalumab treatment

  PD response is achieved if a patient achieves either 1) a 30% increase in PD-1+ T cells in the peripheral blood in subjects who have a minimum of 25 cells/microliter (uL) 9 at baseline, or 2) an absolute increase of at least 75 PD-1+ T cells/uL in subjects who do not have a minimum of 25 PD-1+ T cells/uL at baseline.

  up to 10 days post-enrollment.

Secondary Outcomes (2)

• Safety including adverse events (AEs) and lab values

  Up to 2 years post-enrollment.

• Overall response (OR)

  Up to 5 years post-enrollment.

Study Arms (1)

Treatment

EXPERIMENTAL

Subjects will receive 1 cycle of tremelimumab/durvalumab * Subjects will undergo resection to obtain tumor for generation of autologous tumor infiltrating lymphocytes (TIL) cultures and blood draw to obtain peripheral blood mononuclear cell (PBMC)s * TIL and PBMC will undergo immunoselection based on binding to an anti-programmed cell death 1 (PD-1) antibody and then will be expanded ex vivo. Subjects will receive 3 cycles of ipilimumab/nivolumab • Subjects will undergo staging with computer tomography (CT) chest/abdomen/pelvis and brain magnetic resonance imaging (MRI) or CT scan. subjects with stable disease will continue with nivolumab monotherapy; Subjects with progressive disease will proceed to cell therapy.

Drug: tremelimumab/durvalumab, ipilimumab/nivolumab and nivolumab monotherapy

Interventions

tremelimumab/durvalumab, ipilimumab/nivolumab and nivolumab monotherapy DRUG

Subjects will receive 1 cycle of tremelimumab/durvalumab * Subjects will undergo resection to obtain tumor for generation of autologous tumor infiltrating lymphocytes (TIL) cultures and blood draw to obtain peripheral blood mononuclear cell (PBMC)s * TIL and PBMC will undergo immunoselection based on binding to an anti-programmed cell death 1 (PD-1) antibody and then will be expanded ex vivo. Subjects will receive 3 cycles of ipilimumab/nivolumab • Subjects will undergo staging with computer tomography (CT) chest/abdomen/pelvis and brain magnetic resonance imaging (MRI) or CT scan. subjects with stable disease will continue with nivolumab monotherapy; Subjects with progressive disease will proceed to cell therapy.

Treatment

Eligibility Criteria

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

You may qualify if:

• Untreated metastatic melanoma
• A metastatic lesion at least 1.5 cm in diameter that can be removed surgically
• Measurable or evaluable disease not including the resected lesion; at least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to enrollment
• Capable of giving signed informed consent
• Age \>18 years at time of screening
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Body weight \>30 kg
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC ≥1.0 x 109/L (\> 1000 per mm3)
• Absolute lymphocyte count (ALC ≥0.5 x 109/L (\> 500 per mm3) Platelet count ≥100 (or 75) x 109/L (\>75,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert's syndrome)
• Aspartate aminotransferase (AST) (SGOT)/Alanine aminotransferase (ALT) (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

You may not qualify if:

• Received prior treatment for metastatic melanoma
• Received prior cell transfer therapy that included non-myeloablative or ablative chemotherapy
• Received anti PD-1 immune therapy within prior 6 months
• Any contraindication to neutropenia or thrombocytopenia for up to 2 weeks (no active major infection, no site of active, clinically significant bleeding)
• Concurrent major medical illnesses
• Any form of immunodeficiency
• Severe hypersensitivity to any of the agents used in this study
• Contraindications for IL-2 administration
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Participation in another clinical study with an investigational product during the last 4 weeks
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab, tremelimumab, ipilimumab or nivolumab may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.

Sponsors & Collaborators

• Yale University: lead
• AstraZeneca: collaborator

MeSH Terms

Conditions

Melanoma

Interventions

tremelimumab; durvalumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Michael Hurwitz, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: January 10, 2020
• Study Start: August 15, 2020
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2025
• Last Updated: November 22, 2021

Record last verified: 2021-11