Inclusion Criteria:
1. Ability to understand and provide informed consent.
2. Willingness and ability to comply with scheduled study visits and procedures.
3. Adult men or women age ≥ 18 years.
4. ECOG performance status of 0 or 1.
5. Part 1 monotherapy: Advanced/metastatic NSCLC, cSCC, Merkel cell, melanoma, TNBC,
pancreatic cancer, or head and neck cancer.
6. Part 2 MEM-288 plus nivolumab combination: Advanced/metastatic NSCLC which has
progressed following front-line anti-PD-1/PD-L1 with or without concurrent
chemotherapy. No more than one prior line of therapy for advanced/metastatic disease.
7. Per each tumor type shown below, the specific initial standard of care therapies after
which the subjects with specific histologies must have progressed have been included.
Subjects will have been treated with at least one or more than one line of therapy
prior to enrollment in the study.
1. Non-small cell lung cancer (NSCLC)
Part 1 monotherapy.
- - Must have progressed on standard therapy, including platinum-based
chemotherapy and checkpoint inhibitor therapy (combined or sequential).
- - Patients with tumors that have known actionable molecular alteration such in
EGFR, ALK, ROS-1, BRAF, RET, MET, and KRAS must have progressed on standard
directed molecular therapy, and platinum-based chemotherapy.
Part 2 MEM-288 plus nivolumab combination.
- - Must have first progression more than (>) 84 days following initiation
(cycle 1 day 1) of their most recent anti-PD-1 or PD-L1 checkpoint inhibitor
therapy with or without concurrent chemotherapy.
2. Cutaneous squamous-cell carcinoma (cSCC)
- - Must have progressed on standard therapy, including platinum-based
chemotherapy and/or checkpoint inhibitor therapy.
3. Merkel cell Carcinoma.
- - Must have progressed on standard checkpoint inhibitor therapy.
4. Melanoma.
- - Subjects must have received a BRAF inhibitor as monotherapy or in
combination with other targeted agents for BRAF V600E mutant melanoma.
- - Subjects must have received an anti-PD-1/ PD-L1inhibitor as monotherapy or
combination with anti-CTLA-4 inhibitor or other therapies.
5. Pancreatic cancer.
- - Progression after systemic chemotherapy which included either gemcitabine or
Fluorouracil (5-FU)-based regimen (including capecitabine).
6. Triple negative breast cancer (TNBC)
- - Prior treatment (for advanced, metastatic or (neo)adjuvant) must have
included a taxane and/or anthracycline-based therapy.
7. Head and Neck Cancer.
- - Prior treatment requirement in the metastatic or unresectable locally
advanced setting include:
- Subjects must have received a platinum containing chemotherapy regimen for
treatment of primary tumor in locally advanced, or metastatic settings.
- - Subjects must have received an anti-PD-1/ PD-L1 as monotherapy or in
combination with chemotherapy.
8. Progressed following therapy with at least one PD-1 or PD-L1 checkpoint inhibitor
(regardless of PD-L1 expression status), except for patients with pancreatic cancer.
a) Prior progression on a PD-1 or PD-L1 checkpoint inhibitor should be unequivocal;
progression that occurs within the first 8 weeks of treatment on these agents should
be confirmed with a second CT at least 4 weeks apart (to exclude pseudo-progression).
9. Patients with activating EGFR mutation or ALK rearrangement which is expected to be
responsive to available tyrosine kinase inhibitor therapy, must have been previously
treated with an applicable tyrosine kinase inhibitor.
10. Tumor lesion which is deemed feasible for biopsy and injection under CT or ultrasound
guidance (based on size, location, and visibility) by an interventional radiologist,
and patient willing and able to provide tissue from biopsy of this lesion. Injected
tumor should be > 1 cm3 in volume and should not encase or be inseparable from vital
structures such as major nerves or blood vessels.
a) For Part 1 monotherapy patients treated at the first dose level, the tumor for
injection must be an accessible cutaneous, subcutaneous, or superficial lymph node
lesion that is palpable.
11. Measurable disease, as defined per RECIST version 1.1.
12. Prior history of brain metastases are eligible, provided:
1. Brain metastases have been treated. 2. Asymptomatic from the brain metastases. 3. Corticosteroids prescribed for the management of brain metastases have been
discontinued at least 7 days before registration to study. 4. Brain metastases are stable on pre-registration imaging. 5. No evidence of leptomeningeal disease. 13. Life expectancy > 3 months.
14. Adequate organ and marrow function as defined below:
1. Absolute neutrophil count (ANC) ≥1.5 x 10^9/L. 2. Hemoglobin ≥90 g/L (or ≥9 g/dL)
3. Platelets ≥100 x 10^9/L. 4. Calculated creatinine clearance of >50 mL/min using Cockcroft Gault equation. 5. Total bilirubin ≤ 1.5 x institutional upper limit of normal. 6. AST (SGOT) and ALT (SGPT) ≤2.5 x institutional upper limit of normal. 7. If Alkaline Phosphatase ≥ 2.5 x institutional upper limit of normal, then AST and
ALT must be ≤ 1.5 x institutional upper limit of normal. 15. Patients of childbearing age must not be pregnant and must use established
contraceptive strategies:
1. Female subjects of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.
2. Female subjects of childbearing potential should be willing to use 2 methods of
birth control or be surgically sterile, or abstain from heterosexual activity for
the course of the study through 120 days after the last dose of study medication.
Subjects of childbearing potential are those who have not been surgically
sterilized or have not been free from menses for > 1 year.
3. Male subjects should agree to use an adequate method of barrier contraception
starting with the first dose of study therapy through 120 days after the last
dose of study therapy.
Exclusion Criteria:
1. Pregnant or breast feeding.
2. Serious uncontrolled medical disorder, psychiatric condition or laboratory
abnormalities that, in the opinion of the investigator, may increase the risk
associated with study participation or may interfere with the interpretation of study
results.
3. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), or significant
traumatic injury, within 4 weeks prior to starting study treatment or has not
recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS)
and mediastinoscopy are exceptions and patients can receive study treatment ≥1 week
after these procedures.
4. History of clinically significant noninfectious interstitial pneumonitis (i.e.,
limiting activities of daily living or requiring therapeutic intervention), including
clinically significant radiation pneumonitis.
5. Residual toxicity from prior anticancer therapy of grade 3 or greater (CTCAE v5.0),
with the exception of alopecia.
6. Concurrent use of other anticancer approved or investigational agents.
7. Clinically significant, uncontrolled heart disease and/or recent cardiac event (within
6 months), such as:
1. unstable angina within 6 months prior to screening. 2. myocardial infarction within 6 months prior to screening. 3. history of documented congestive heart failure (New York Heart Association
functional classification III-IV)
4. cardiac arrhythmias not controlled with medication. 8. Active autoimmune disease requiring disease modifying therapy (except vitiligo,
Grave's, or psoriasis not requiring systemic treatment).
9. Any form of active primary or secondary immunodeficiency.
10. Receiving ≥10 mg daily prednisone (or equivalent).
11. Prior malignancy (except non-melanoma skin cancers, and the following in situ cancers:
bladder, gastric, colon, cervical/dysplasia endometrial, melanoma, or breast) are
excluded unless a complete remission was achieved at least 2 years prior to study
entry AND no additional therapy is required or anticipated to be required during the
study period.
12. Active systemic infections requiring intravenous antibiotics.
13. Prior therapy with anti-tumor vaccines or other immune-stimulatory antitumor agents
(other than FDA approved and National Comprehensive Cancer Network [NCCN] recommended
systemic therapies).
14. Prisoners or subjects who are involuntarily incarcerated, or who are compulsorily
detained for treatment of either a psychiatric or physical illness.
15. Any unresolved grade 2 irAE (except adequately treated endocrine irAE).
16. Any toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1
immunotherapy.
