A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

NCT02521870 | Terminated Phase 1 Results DMC

• 3 other identifiers: DV3-MEL-01Keynote 184SYNERGY-001
• Study Type: interventional
• Target: 241
• Locations: 4 countries
• Sites: 47

Brief Summary

This is a phase 1b/2, open-label, multicenter trial designed to evaluate the safety, tolerability, biologic activity, and preliminary efficacy of intratumoral SD-101 injections in combination with intravenous pembrolizumab in patients with metastatic melanoma or recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). This study will be conducted in 2 phases. Phase 1 evaluates SD-101 given in combination with pembrolizumab in melanoma populations (anti-PD-1/L1 naïve and anti-PD-1/L1 experienced with progressive disease) in up to 4 Dose Escalation cohorts to identify a recommended Phase 2 dose (RP2D) to be evaluated in up to 4 Dose Expansion cohorts in Phase 2. Phase 2 also includes up to 4 Dose Expansion cohorts of patients with HNSCC (anti-PD-1/L1 naïve and anti-PD-1/L1 experienced with progressive disease).

Conditions

Metastatic Melanoma; Head Neck Cancer

Keywords

Skin Cancer; Skin Tumors; Head and Neck Squamous Cell Carcinoma; Cancer Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Phase 1 Dose Escalation Only - Number of Participants With DLTs

  Dose-limiting toxicities (DLTs) are defined per protocol as specific AEs occurring from the time of the first injection (Day 1) through Day 29.

  Day 1 through Day 29

• Phase 1 Dose Escalation and Phase 2 Dose Expansion - Overall Response Rate (ORR) by Analysis Group

  Overall response rate (ORR) by analysis group based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 was evaluated from Baseline (Day 1) through Day 743 or End of Study (EOS).

  Day 1 through Day 743

Secondary Outcomes (4)

• Phase 1 Dose Escalation and Phase 2 Dose Expansion - Time to Objective Response by Analysis Group

  Day 1 through Day 743

• Phase 1 Dose Escalation and Phase 2 Dose Expansion - Duration of Response by Analysis Group

  Day 1 through Day 743

• Phase 1 Dose Escalation and Phase 2 Dose Expansion - Disease Control Rate (DCR) by Analysis Group

  Day 1 through Day 743

• Phase 1 Dose Escalation and Phase 2 Dose Expansion - Progression-Free Survival Rate by Analysis Group

  Day 1 through Day 743

Study Arms (9)

Dose Escalation Phase 1b

EXPERIMENTAL

Determine the maximum tolerated dose (MTD) of escalating doses of SD-101(1) administered in combination with pembrolizumab in patients with melanoma (anti-PD-1/L1 therapy naïve and experienced patients with progressive disease).

Drug: SD-101(1); Biological: Pembrolizumab

Dose Expansion Phase 2 (Cohort 1)

EXPERIMENTAL

Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent or metastatic melanoma.

Drug: SD-101(2); Biological: Pembrolizumab

Dose Expansion Phase 2 (Cohort 2)

EXPERIMENTAL

Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy progressing patients with recurrent or metastatic melanoma.

Drug: SD-101(2); Biological: Pembrolizumab

Dose Expansion Phase 2 (Cohort 3)

EXPERIMENTAL

Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent head and neck squamous cell carcinoma.

Drug: SD-101(2); Biological: Pembrolizumab

Dose Expansion Phase 2 (Cohort 4)

EXPERIMENTAL

Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy progressing patients with recurrent head and neck squamous cell carcinoma.

Drug: SD-101(2); Biological: Pembrolizumab

Dose Expansion Phase 2 (Cohort 5)

EXPERIMENTAL

Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent or metastatic melanoma.

Biological: SD-101(3); Biological: Pembrolizumab

Dose Expansion Phase 2 (Cohort 6)

EXPERIMENTAL

Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent head and neck squamous cell carcinoma.

Biological: SD-101(3); Biological: Pembrolizumab

Dose Expansion Phase 2 (Cohort 7)

EXPERIMENTAL

Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy refractory or resistant patients with recurrent head and neck squamous cell carcinoma.

Biological: SD-101(3); Biological: Pembrolizumab

Dose Expansion Phase 2 (Cohort 8)

EXPERIMENTAL

Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy refractory or resistant patients with recurrent or metastatic melanoma.

Biological: SD-101(3); Biological: Pembrolizumab

Interventions

SD-101(1) DRUG

SD-101 administered intratumorally at escalating doses (up to 11 doses).

Dose Escalation Phase 1b

Pembrolizumab BIOLOGICAL

Pembrolizumab administered intravenously, 200 mg Q3W for two years (up to 35 doses).

Dose Escalation Phase 1b

SD-101(2) DRUG

Dose Q1W for 4 weeks followed by dose Q3W for 7 weeks, then 9 weeks off, then dose Q1W for 4 weeks followed by dose Q3W for 7 weeks (up to 22 total doses).

Dose Expansion Phase 2 (Cohort 1); Dose Expansion Phase 2 (Cohort 2); Dose Expansion Phase 2 (Cohort 3); Dose Expansion Phase 2 (Cohort 4)

SD-101(3) BIOLOGICAL

Dose Q1W for 4 weeks followed by dose Q3W for 16 additional weeks (up to 20 total doses).

Dose Expansion Phase 2 (Cohort 5); Dose Expansion Phase 2 (Cohort 6); Dose Expansion Phase 2 (Cohort 7); Dose Expansion Phase 2 (Cohort 8)

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent for the trial
• Aged 18 years and older
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
• Patient must have adequate organ function as indicated by the following laboratory values:
• Hematological:
• Absolute neutrophil count (ANC) ≥ 1,500 /mcL
• Platelet count ≥ 100,000 /mcL
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
• Renal:
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN) OR
• Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥ 60 mL/min for subject with creatinine levels \> 1.5 × institutional ULN
• Hepatic:
• Serum total bilirubin:
• ≤ 1.5 × ULN OR
• \< 3 × ULN for persons with Gilbert's syndrome OR

You may not qualify if:

• Received systemic chemotherapy or biological cancer therapy (except anti-PD-1/L1 therapy) within 3 weeks prior to study enrollment
• Received prior radiotherapy within 2 weeks of start of study therapy. A shorter washout period may be permitted after approval by the Medical Monitor.
• Received small molecule inhibitor targeted therapy, such as tyrosine kinase inhibitors, within 2 weeks prior to study enrollment
• Has not recovered to CTCAE Grade 1 or better from the AEs due to cancer therapeutics prior to study enrollment
• NOTE: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia or Grade 2 AEs that qualify as Grade 2 due to replacement hormonal or steroid therapy are exceptions to this criterion and may qualify for the study with approval by a Dynavax Medical Monitor.
• If a patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to enrollment.
• Received a transfusion of blood products (including platelets or red blood cells) or colony-stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study enrollment
• Is expected to require any other form of anti-cancer therapy while in the trial
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy (including immune modulators or systemic corticosteroids) within 7 days prior to study enrollment
• Positive for active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection as determined by laboratory tests for HBsAg, anti-HBc, and anti-HBs; anti-HCV; and anti-HIV -1/2, respectively
• History of or current uveal or ocular or mucosal melanoma
• Active infection including cytomegalovirus
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of trial treatment
• Active autoimmune disease requiring systemic treatment in the past 2 years or a disease that requires immunosuppressive medication including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Current pneumonitis or history of (non-infectious) pneumonitis that required steroids

Sponsors & Collaborators

• Dynavax Technologies Corporation: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (47)

University of Alabama School of Medicine

Birmingham, Alabama, 35294, United States

Location

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85721, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford Hospitals and Clinics

Palo Alto, California, 94305, United States

Location

University of California, San Diego

San Diego, California, 92093, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Georgia Cancer Center - Northside Hospital Central Research Department

Atlanta, Georgia, 30341, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

University of Iowa Healthcare

Iowa City, Iowa, 52242, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68130, United States

Location

Atlantic Health

Morristown, New Jersey, 07962, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Cleveland Medical Center - Seidman Cancer center

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

University of Utah Health Care - Huntsman Cancer institute

Salt Lake City, Utah, 84112, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

The Tweed Hospital

Tweed Heads, New South Wales, 2485, Australia

Location

Liverpool Hospital

Westmead, New South Wales, 2170, Australia

Location

Melanoma Institute

Wollstonecraft, New South Wales, 2065, Australia

Location

Adelaide Cancer Centre - Ashford Cancer Centre

Kurralta Park, South Australia, 5037, Australia

Location

Hollywood Private Hospital / Affinity Research

Nedlands, Western Australia, Australia

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Klinikum BuxtehudeDermato-Onkologie Studienzentrale

Buxtehude, Germany

Location

Uniklinikum Dresden Klinik und Poliklinik für Dermatologie

Dresden, Germany

Location

Universitätshautklinik Frankfurt

Frankfurt, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

HNO-Universitätsklinik Jena

Jena, Germany

Location

Universitätshautklinik Magdeburg

Magdeburg, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Christchurch Hospital

Christchurch, 4710, New Zealand

Location

Waikato Hospital

Hamilton, 3204, New Zealand

Location

Related Publications (1)

• Ribas A, Medina T, Kummar S, Amin A, Kalbasi A, Drabick JJ, Barve M, Daniels GA, Wong DJ, Schmidt EV, Candia AF, Coffman RL, Leung ACF, Janssen RS. SD-101 in Combination with Pembrolizumab in Advanced Melanoma: Results of a Phase Ib, Multicenter Study. Cancer Discov. 2018 Oct;8(10):1250-1257. doi: 10.1158/2159-8290.CD-18-0280. Epub 2018 Aug 28.

  PMID: 30154193 DERIVED

MeSH Terms

Conditions

Melanoma; Head and Neck Neoplasms; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The sponsor terminated the trial early due to strategic restructuring, including the planned conclusion of clinical oncology development programs and no further sponsoring of the development of SD-101.

Results Point of Contact

• Title: Robert Janssen MD \ VP & Chief Medical Officer
• Organization: Dynavax Technologies, Inc.

rjanssen@dynavax.com

510-665-0414

Study Officials

• Antoni Ribas, MD

  UCLA School of Medicine (Melanoma)

  PRINCIPAL INVESTIGATOR

• Ezra Cohen, MD

  UCSD Moores Cancer Center (HNSCC)

  PRINCIPAL INVESTIGATOR

• Thomas Tüting, MD

  University Hospital Magdeburg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 13, 2015
• Study Start: September 1, 2015
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: August 3, 2021
• Results First Posted: August 3, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share

Locations

DE (9); AU (5); NZ (3); US (30)