| Eligibility |
[Inclusion Criteria (Phase 1 and Phase 2)]
1. Willing and able to provide written informed consent for the trial
2. Aged 18 years and older
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
4. Patient must have adequate organ function as indicated by the following laboratory
values:
1. Hematological:
- Absolute neutrophil count (ANC) = 1,500 /mcL
- Platelet count = 100,000 /mcL
- Hemoglobin = 9 g/dL or = 5.6 mmol/L
2. 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
3. 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
4. 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
5. Have provided 2 tissue biopsy samples taken of the target lesion (Lesion A) 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 of the
anticipated target lesion that has been collected within 3 months of screening. The
other sample is for RNA expression profiling and must be a fresh biopsy.
6. Life expectancy of at least 6 months
7. Female patients of childbearing potential, as defined in Section 5.2.1, must have a
negative urine or serum pregnancy test within 72 hours prior to taking the first dose
of trial treatment. If the urine test is positive or cannot be confirmed as negative
then a serum test is required which must be negative for the patient to enroll. Women
of childbearing potential (WOCBP) must be willing to use 2 medically acceptable
methods of contraceptive from Day 1 through 120 days after the last dose of trial
treatment. The 2 medically acceptable birth control methods can be either 2 barrier
methods or a barrier method plus a hormonal method to prevent pregnancy. The following
are considered adequate barrier methods of contraception: diaphragm, condom (by the
partner), copper intrauterine device, sponge, or spermicide as per local regulations
or guidelines. Appropriate hormonal contraceptives will include any registered and
marketed contraceptive agent that contains an estrogen and/or a progestational agent
(including oral, subcutaneous, intrauterine, or intramuscular agents).
Male patients of reproductive potential, as described in Section 5.2.1, must agree to
use an adequate method of contraception from Day 1 through 120 days after the last
dose of trial treatment.
Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the patient.
[Inclusion Criteria (Phase 1 only: Melanoma)]
8. Histologically or cytologically confirmed unresectable or metastatic (stage IV)
melanoma
9. For Phase 1 Escalation Cohorts 1-4, must have at least 1 lesion that qualifies as a
target lesion per RECIST v1.1 except for the minimum measurement of 10 mm in diameter
for superficial lesions, is easily accessible (palpable or can be visualized by
ultrasound), and is amenable to multiple intratumoral injections. If superficial, the
target lesion must be documented photographically.
[Inclusion Criteria (Phase 2 only: Melanoma)]
10. Histologically or cytologically confirmed recurrent or unresectable or metastatic
(stage IV) melanoma
11. 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. If superficial, the target lesion must
measure at least 10 mm in diameter, be measured by calipers, and be documented
photographically. Tumor lesions situated in a previously irradiated area, or in an
area subjected to other loco-regional therapy, are usually not considered measurable
unless there has been demonstrated progression in the lesion. Approval from the
Medical Monitor is required to inject a previously radiated lesion.
12. Expansion Cohort 2: Must have documented PD per RECIST v1.1 on a prior treatment
regimen containing an anti-PD-1/L1 drug (see Appendix 6 for definition of PD per
RECIST v1.1)
13. Expansion Cohort 8: Must have all of the following:
1. Received at least 2 doses of an anti-PD-1/L1 therapy
2. PD occurred within 3 months after last dose of anti-PD-1/L1 therapy
3. 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)]
14. Histologically or cytologically confirmed recurrent or metastatic HNSCC that could not
be treated with curative intent
15. 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. Tumor lesions situated in a previously irradiated
area, or in an area subjected to other loco-regional therapy, are usually not
considered measurable unless there has been demonstrated progression in the lesion.
Approval from the Medical Monitor is required to inject a previously radiated lesion.
16. Expansion Cohort 4: Must have documented confirmed PD per RECIST v1.1 on a prior
treatment regimen containing an anti-PD-1/L1 drug (see Appendix 6 for definition of PD
per RECIST v1.1)
17. Expansion Cohort 7: Must have all of the following:
1. 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)
2. 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
3. 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
[Exclusion Criteria (Phase 1 and Phase 2)]
1. Received systemic chemotherapy or biological cancer therapy (except anti-PD-1/L1
therapy) within 3 weeks prior to study enrollment
2. Received prior radiotherapy within 2 weeks of start of study therapy. A shorter
washout period may be permitted after approval by the Medical Monitor.
3. Received small molecule inhibitor targeted therapy, such as tyrosine kinase
inhibitors, within 2 weeks prior to study enrollment
4. 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.
5. 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
6. Is expected to require any other form of anti-cancer therapy while in the trial
7. 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
8. 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
9. History of or current uveal or ocular or mucosal melanoma
10. Active infection including cytomegalovirus
11. 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
12. 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.
13. Current pneumonitis or history of (non-infectious) pneumonitis that required steroids
14. 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.
15. Known active central nervous system metastases or carcinomatous meningitis
NOTE: Patients with previously treated brain metastases may participate provided they
are stable (without evidence of progression by imaging [using the identical imaging
modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the
first dose of trial treatment and with any neurologic symptoms returned to baseline),
have no evidence of new or enlarging brain metastases, and are not using steroids for
at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.
16. Use of any investigational agent within the last 28 days prior to study enrollment
17. Has received a live-virus vaccination within 30 days of planned treatment start.
Seasonal flu vaccines that do not contain live virus are permitted.
18. 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
19. History of sensitivity to any component of SD-101 or hypersensitivity reaction to
treatment with a monoclonal antibody and/or any of its excipients
20. 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)]
21. Melanoma considered resectable with curative intent
22. Prior therapy with an anti-PD-1/L1 agent
23. Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients
[Exclusion Criteria (Phase 2, Melanoma Expansion Cohorts 2 and 8 only)]
24. Melanoma considered resectable with curative intent
25. 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)]
26. HNSCC considered resectable with curative intent
27. Prior therapy with an anti-PD-1/L1 agent
28. Require anticoagulation therapy
[Exclusion Criteria (Phase 2, HNSCC Expansion Cohorts 4 and 7 only)]
29. HNSCC considered resectable with curative intent
30. 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
31. Require treatment on anticoagulation therapy
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