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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

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ClinicalTrials.gov Identifier: NCT02521870
Recruitment Status : Recruiting
First Posted : August 13, 2015
Last Update Posted : June 5, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Dynavax Technologies Corporation

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).

Phase 1 of this trial is a modified 3+3 dose escalation study evaluating escalating or intermediate dose levels of SD-101 given with a fixed dose of pembrolizumab in patients with metastatic melanoma.

Phase 2 of this study will consist of 7 expansion cohorts to further evaluate the efficacy and safety of SD-101 given in combination with pembrolizumab in specific melanoma and HNSCC populations: For each of the indications in melanoma and HNSCC 2 separate cohorts will be recruited, those who are anti-programmed death receptor-1/ligand 1 (anti-PD-1/L1) therapy naïve and those who have progressive disease (PD) while receiving anti-PD-1/L1 therapy.


Condition or disease Intervention/treatment Phase
Metastatic Melanoma Head Neck Cancer Drug: SD-101(1) Biological: Pembrolizumab Drug: SD-101(2) Phase 1 Phase 2

Detailed Description:

This study will be conducted in two parts.

Phase 1b is dose escalation in which patients are tested with SD-101 at various doses in combination with 200 mg pembrolizumab in patients with metastatic melanoma.

Phase 2 will consist of 7 expansion cohorts to evaluate the efficacy and safety of SD-101 given in combination with 200 mg pembrolizumab in specific melanoma populations and recurrent or metastatic HNSCC.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 234 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2, Open-label, Multicenter, Dose-escalation and Expansion Trial of Intratumoral SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (SYNERGY-001)
Study Start Date : September 2015
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020


Arm Intervention/treatment
Experimental: Dose Escalation Phase 1b
Determine the MTD of escalating doses of SD-101(1) administered in combination with pembrolizumab.
Drug: SD-101(1)
SD-101 administered intratumorally at escalating doses (up to 11 doses)

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

Experimental: Dose Expansion Phase 2 (1)
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)
SD-101 administered intratumorally (up to 22 doses)

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

Experimental: Dose Expansion Phase 2 (2)
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)
SD-101 administered intratumorally (up to 22 doses)

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

Experimental: Dose Expansion Phase 2 (3)
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)
SD-101 administered intratumorally (up to 22 doses)

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

Experimental: Dose Expansion Phase 2 (4)
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)
SD-101 administered intratumorally (up to 22 doses)

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




Primary Outcome Measures :
  1. Phase 1b - Incidence of dose-limiting toxicities (DLTs). [ Time Frame: Day 29 ]
    DLTs evaluated through 7 days after last dose

  2. Phase 2 To assess the tumor response both locally and systemically of injected lesions, non-injected lesions, and all lesions. [ Time Frame: Day 743 ]
    Evaluated through Day 743


Secondary Outcome Measures :
  1. Phase 2 - Incidence of injection-site reactions, adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Day 743 ]
    Evaluated through Day 743

  2. Phase 2 - Time to objective response (TOR) per RECIST 1.1 [ Time Frame: Day 743 ]
    Evaluated through Day 743

  3. Phase 2 - Duration of response per RECIST 1.1 [ Time Frame: Day 743 ]
    Evaluated through Day 743

  4. Phase 2 - Duration of radiographic progression-free survival (PFS) per RECIST 1.1 [ Time Frame: Day 743 ]
    Evaluated through Day 743



Information from the National Library of Medicine

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

Inclusion Criteria (Phase 1 and 2 Melanoma and HNSCC patients)

  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
  • Life expectancy of at least 6 months.
  • Have provided tissue biopsy sample enough for PD-L1 expression level testing and RNA expression profiling.

Inclusion Criteria: Phase 2 Melanoma patients

  • Histologically or cytologically confirmed unresectable or metastatic (stage IV) melanoma.
  • Have at least 2 sites that qualify as measurable target lesions per RECIST 1.1 of which 1 must be palpable or visualized by ultrasound and easily accessible to multiple intratumoral injections.
  • For patients with progressive disease (PD) while receiving anti-PD-1/L1 therapy, must have documented PD per RECIST v1.1 while receiving a prior anti-PD-1/L1 therapy.

Inclusion Criteria: Phase 2 HNSCC patients

  • Histologically or cytologically confirmed recurrent or metastatic HNSCC that could not be treated with curative intent.
  • Have at least 1 measurable target lesion per RECIST 1.1, which must be accessible and amenable to multiple intratumoral injections.
  • Must have documented PD per RECIST v1.1 while receiving a prior anti-PD-1/L1 therapy.

Exclusion Criteria: (Phase 1 and 2 Melanoma and HNSCC patients)

  • 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.
  • Received small molecule inhibitor targeted therapy, such as tyrosine kinase inhibitors, within 2 weeks prior to study enrollment.
  • 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
  • Is expected to require any other form of anti-cancer therapy while in the trial.
  • Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
  • History of or current uveal or ocular melanoma.
  • Active infection including cytomegalovirus.
  • Active autoimmune disease requiring systemic treatment in the past 2 years or a disease that requires immunosuppressive medication. Replacement therapy is not considered a form of systemic treatment.
  • Current pneumonitis or history of (non-infectious) pneumonitis that required steroids.
  • Known active central nervous system metastases or carcinomatous meningitis.
  • Use of any investigational agent within the last 28 days prior to study enrollment.
  • Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
  • Any known additional malignancy that is progressing or requires active treatment, except for melanoma and HNSCC.

Exclusion Criteria (Phase 2, Melanoma Expansion Cohorts 1 and 5 only)

  • Any prior combination therapy targeting immunoregulatory receptors or mechanisms and an anti-PD-1/L1 agent or an investigational agent targeting immunoregulatory receptors
  • Prior therapy with an anti PD 1/L1 agent

Exclusion Criteria: (Phase 2, Melanoma Expansion Cohort 2 only)

• Any prior combination therapy involving agents given by intratumoral injection that target the innate immune pathway or system.

Exclusion Criteria: (Phase 2, HNSCC Expansion Cohorts 3 and 6 only)

  • Prior therapy with an anti PD 1/L1 agent
  • Require treatment on anticoagulation therapy.

Exclusion Criteria (Phase 2, HNSCC Expansion Cohorts 4 and 7 only)

  • Any prior combination therapy involving agents given by intratumoral injection that target the innate immune pathway or system.
  • Require treatment on anticoagulation therapy

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 ClinicalTrials.gov identifier (NCT number): NCT02521870


Contacts
Contact: Erick Gamelin, MD 510-665-0470
Contact: Robert Janssen, MD 510-665-0414

  Show 45 Study Locations
Sponsors and Collaborators
Dynavax Technologies Corporation
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Antoni Ribas, MD UCLA School of Medicine (Melanoma)
Principal Investigator: Ezra Cohen, MD UCSD Moores Cancer Center (HNSCC)

Responsible Party: Dynavax Technologies Corporation
ClinicalTrials.gov Identifier: NCT02521870     History of Changes
Other Study ID Numbers: DV3-MEL-01
Keynote 184 ( Other Identifier: Merck )
SYNERGY-001 ( Other Identifier: Dynavax )
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: June 5, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be shared under guidance of the New Rule - FDAAA 801 eff. Jan 2017. 3/2017 - additional changes forthcoming.

Keywords provided by Dynavax Technologies Corporation:
Skin Cancer
Skin Tumors
Head and Neck Squamous Cell Carcinoma
Cancer Immunotherapy

Additional relevant MeSH terms:
Carcinoma
Melanoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Neoplasms by Site
Pembrolizumab
Antineoplastic Agents