A Phase II Trial of PD-L1 Therapy Combined With Anti-VEGF Therapy in Unresectable or Metastatic Melanoma

NCT04356729 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-604
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying a combination of two drugs that change the immune system and tumor as a possible treatment for metastatic or unresectable stage III or IV cutaneous melanoma. The names of the study drugs involved in this study are:

• Atezolizumab
• Bevacizumab

Conditions

Clinical Stage III Cutaneous Melanoma AJCC v8; Stage IV Melanoma; Unresectable Stage III Cutaneous Melanoma; Unresectable Stage IV Cutaneous Melanoma

Keywords

Metastatic stage III cutaneous melanoma; Metastatic stage IV cutaneous melanoma; Unresectable stage III cutaneous melanoma; Unresectable stage IV cutaneous melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate in PD-L1 negative melanoma

  The primary endpoint for this study is overall response rate in PDL1 negative melanoma to combination anti-PD-L1 therapy and anti-VEGF therapy by RECIST criteria. The proportion of patients with complete response or partial response as best response to therapy will be summarized and presented with a two-sided, 90% Wald confidence interval.

  5 Years

Secondary Outcomes (5)

• Overall survival

  start of treatment and death from any cause up to 5 years

• Time to tumor progression

  up to 5 years

• Duration of response

  patients with objective response (confirmed CR or PR as best overall response) as the interval between dates of first documentation of objective response and first documentation of progressive disease up to 5 years

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE 5.

  initiation of study treatment, during study treatment, and 30 days after the last dose of study treatment or study discontinuation/termination, whichever occurs first up to 5 years

• Change tumor-infiltrating lymphocytes (TILs)

  baseline and progression/treatment discontinuation up to 5 years

Study Arms (1)

Atezolizumab and Bevacizumab

EXPERIMENTAL

The research study procedures include screening for eligibility, study treatment including evaluations, a biopsy, and follow up visits. * Atezolizumab will be administered intravenously at a fixed predetermined dose every three weeks * Bevacizumab will be administered intravenously at a fixed predetermined dose every three weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis Study treatment will continue until study doctors decide to stop therapy due to criteria which may include disease progression, adverse events or changes in condition. Participants will be followed for survival health information following treatment until the study ends, which could be approximately 5 years from start of treatment

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

Atezolizumab will be administered intravenously at a fixed predetermined dose every three weeks ith 21 consecutive days defined as a treatment cycle.

Also known as: Tecentriq

Atezolizumab and Bevacizumab

Bevacizumab DRUG

Bevacizumab will be administered intravenously at a fixed predetermined dose every three weeks, with 21 consecutive days defined as a treatment cycle.

Also known as: Avastin, Mvasi

Atezolizumab and Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed metastatic or unresectable stage III or IV cutaneous melanoma.
• PD-L1 negative staining in at least one biopsy sample.
• Age ≥ 18 years
• ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A)
• Participants may have received any number of prior therapies for treatment of their cutaneous melanoma, excluding prior treatment with anti-PD-L1 therapeutic antibodies or bevacizumab.
• Participants must have measurable disease per RECIST v1.1.
• Participants must have availability of a representative tumor specimen for exploratory biomarker research.
• Participants must have normal organ and marrow function as defined below:
• lymphocyte count ≥ 500/mcL
• absolute neutrophil count ≥ 1,500/mcL without granulocyte colony-stimulating factor support
• platelets\* ≥100,000/mcL
• hemoglobin\* ≥9 g/dL
• serum bilirubin ≤1.5 x ULN with the following exception: participants with known Gilbert's Disease: serum bilirubin level ≤ 3x ULN
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN, with the following exceptions: Participants with documented liver metastases: AST and ALT ≤ 5 x ULN
• alkaline phosphatase (ALP) ≤2.5 × institutional ULN, with the following exceptions:

You may not qualify if:

• Participants with symptomatic, untreated, or actively progressing CNS metastases will be excluded. If a participant has a known history of treated CNS lesions, they are eligible provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS.
• The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
• Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
• There is no evidence of interim progression between completion of CNS-directed therapy and the screening brain scan
• The participant has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment.
• The participant has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted. Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.
• History of leptomeningeal disease.
• Uncontrolled tumor-related pain.
• NOTE: Participants requiring pain medication must be on a stable regimen at study entry.
• Symptomatic lesions amendable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment. Participants should be recovered from the effects of radiation. There is no required minimum recovery period.
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab and/or bevacizumab.
• Uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome,Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions:

Sponsors & Collaborators

• Elizabeth Buchbinder, MD: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

atezolizumab; Bevacizumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Elizabeth Buchbinder, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 22, 2020
• Study Start: August 6, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)