| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Melanoma Cancer or Head and Neck Cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10060121 |
| E.1.2 | Term | Squamous cell carcinoma of head and neck |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10027480 |
| E.1.2 | Term | Metastatic malignant melanoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Phase 1 (Dose Escalation) is closed.
Phase 2 (Dose Expansion) Primary Objectives
•To assess the tumor response both locally and systemically including:
-Treatment response of the injected lesion(s) (local response)
-Treatment response of the non-injected lesion(s) (systemic response)
-Treatment response of all lesions
|
|
| E.2.2 | Secondary objectives of the trial |
Phase 2 (Dose Expansion) Secondary Objectives
• To assess the safety and tolerability of SD-101 in combination with pembrolizumab
• To assess the time frame of tumor responses:
- Time to response
- Duration of response
• To assess progression-free survival (PFS) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Phase 1 study is completed.
A patient must meet all of the following criteria to be eligible for enrollment (defined as receiving the first trial treatment) [ie, pembrolizumab or SD-101]) in the trial:
• 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
• Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 × ULN
• Aspartate transaminase (AST) and alanine transaminase (ALT) (also known as serum glutamic oxaloacetic transaminase and serum glutamic
pyruvic transaminase)
• ≤ 2.5 × ULN OR
• ≤ 5 × ULN for patients with liver metastases
Coagulation
• International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy, and as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy, and as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Have provided 2 tissue biopsy samples taken as a single biopsy split into 2 samples or 2 separate biopsies that meet the minimal sample size requirement per the study laboratory manual. One sample is for determining PD-L1 expression level by immunohistochemistry and can be an archival sample that has been collected within 3 months of screening. The other sample is for RNA expression profiling and must be a fresh biopsy.
• Life expectancy of at least 6 months
• Female patients of childbearing potential, as defined in this protocol, must have a negative urine or serum pregnancy test within 72 hours prior to taking the first dose of trial treatment. Male patient of reproductive potential must agree to use an adequate method of contraception from Day 1 through 120 days after the last dose of trial treatment.
Inclusion Criteria (Phase 2 only: Melanoma)
A patient must meet the following to be eligible for Phase 2 (as applicable to the expansion cohorts):
• Histologically or cytologically confirmed recurrent or unresectable or metastatic (stage IV) melanoma
• Must have at least 2 lesions that qualify as a target lesion per RECIST v1.1, and 1 of the qualifying lesions must be easily accessible (palpable or can be visualized by ultrasound) and amenable to multiple intratumoral injections. The target lesion should be of sufficient size such that the required tumor biopsies do not significantly affect tumor assessment per RECIST v1.1.
• Expansion Cohort 2: Must have documented PD per RECIST v1.1 on a prior treatment regimen containing an anti-PD-1/L1 drug.
•Expansion Cohort 8: Must have all of the following:
a) Received at least 2 doses of an anti-PD-1/L1 therapy, where the last dose of anti-PD-1/L1 therapy was within 6 months of study enrollment (Day 1)
b)Refractory response, ie, PD occurred within 3 months duration of the start of treatment on anti-PD-1/L1 therapy; OR resistant response, ie, PD occurred beyond 3 months duration of treatment on anti-PD-1/L1 therapy and within 6 months after the last dose of treatment on anti-PD-1/L1 therapy
c)Documented PD per RECIST v.1.1, which has been confirmed by a second assessment at least 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression.
Inclusion Criteria (Phase 2 only: HNSCC)
A patient must meet the following to be eligible for Phase 2 (as applicable to the expansion cohorts):
• Histologically or cytologically confirmed recurrent or metastatic HNSCC that could not be treated with curative intent.
• Must have at least 1 lesion that qualifies as a target lesion per RECIST v1.1, and which must be easily accessible (palpable or can be visualized by ultrasound) and amenable to multiple intratumoral injections. The target lesion should be of sufficient size such that the required tumor biopsies do not significantly affect tumor assessment per RECIST v1.1.
• Expansion Cohort 4: Must have documented PD per RECIST v1.1 on a prior treatment regimen containing an anti-PD-1/L1 drug. |
|
| E.4 | Principal exclusion criteria |
A patient with any 1 of the following criteria is not eligible for enrollment in the trial:
• 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 Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics prior to study 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
• An immune-related AE from a previous immunotherapeutic agent that has not resolved to Grade 1 or less prior to study enrollment. The exception is a Grade 2 AE which qualifies as Grade 2 due to replacement steroid therapy which may be allowed with approval by a Dynavax Medical Monitor.
• 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 other significant medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with trial participation or trial drug administration that may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for this trial
• History of sensitivity to any component of SD-101 or hypersensitivity reaction to treatment with a monoclonal antibody and/or any of its excipients
• Any known additional malignancy that is progressing or requires active treatment. Exceptions are cutaneous melanoma or HNSCC under study per protocol, or basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy.
Exclusion Criteria (Phase 2, Melanoma Expansion Cohorts 1 and 5 only)
• Melanoma considered resectable with curative intent
• Prior therapy with an anti-PD-1/L1 agent
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
Exclusion Criteria (Phase 2, Melanoma Expansion Cohorts 2 and 8 only)
• Melanoma considered resectable with curative intent
• Any prior combination therapy involving agents given by intratumoral injection that target the innate immune pathway or system such as oncolytic viral or microbial therapy (eg, T-VEC [talimogene laherparepvec]), toll-like receptors (TLR) agonists, STING or RIG-1 and an anti-PD-1/L1 inhibitor
Exclusion Criteria (Phase 2, HNSCC Expansion Cohorts 3 and 6 only)
• HNSCC considered resectable with curative intent
• Prior therapy with an anti-PD-1/L1 agent
• Require anticoagulation therapy
Exclusion Criteria (Phase 2, HNSCC Expansion Cohorts 4 and 7 only)
• HNSCC considered resectable with curative intent
• Any prior combination therapy involving agents given by intratumoral injection that target the innate immune pathway or system such as oncolytic viral or microbial therapy (eg, T-VEC), TLR agonists, STING or RIG-1 and an anti-PD-1/L1 inhibitor.
• Require treatment on anticoagulation therapy
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Objective response rate (ORR) per RECIST v1.1 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening visit, 9 weeks after the first study injection of SD-101, and then every 9 weeks for the first year and then every 12 weeks for the rest of the study. Screening, Day 64, 127, 190, 253, 316, 379, 463, 547, 631, 715.
[Time Frame: Evaluated through Day 743] |
|
| E.5.2 | Secondary end point(s) |
• Incidence of injection-site reactions, AEs, and SAEs
• Time to response using RECIST v1.1
• Duration of response per RECIST v1.1
• Radiographic PFS per RECIST v1.1
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Incidence of injection-site reactions, adverse events (AEs) and serious adverse events (SAEs)
[Time Frame: Evaluated through Day 743]
• Time to objective response (TOR) per RECIST 1.1
[Time Frame: Evaluated through Day 743]
• Duration of response per RECIST 1.1
[Time Frame: Evaluated through Day 743]
• Duration of radiographic progression-free survival (PFS) per RECIST 1.1
[Time Frame: Evaluated through Day 743]
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Dose escalation / dose expansion |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| New Zealand |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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