| Eligibility |
Inclusion Criteria:
- Written informed consent prior to completing any study-specific procedure
- Dose Escalation and Dose Confirmation Periods: Histologically- or
cytologically-confirmed advanced/metastatic solid tumor or lymphoma by pathology
report and who has received, or been intolerant to, all approved therapies
- Dose Expansion Period: Histologically or cytologically confirmed diagnosis of:
epithelial cancer of the ovary, fallopian tube, or peritoneum which is platinum
resistant or platinum refractory. Participants must have received at least 2 prior
lines of therapy. Participants with known Breast Cancer gene 1 (BRCA) mutation
positive must have been treated with and progressed on at least 1 prior
poly[ADP-ribose] polymerase inhibitor (PARPi)
- Lesions for intratumoral injection and biopsies:
- Dose Escalation: A minimum of one lesion that is easily accessible for injection
where easily accessible is defined as a cutaneous or subcutaneous mass that is
palpable and/or visualizable by ultrasound
- Dose Confirmation: A minimum of one visceral lesion injectable with ultrasound or
computer tomography (CT) guidance and that is not encasing or abutting major
vascular structures or are in a location that are considered high risk for AEs by
the enrolling physician
- Dose Expansion: A minimum of one lesion amenable to injection (either
non-visceral or visceral). Participants must have a tumor lesion amenable to
biopsy and consent to a pre-treatment and an on-treatment biopsy. For
participants with only one lesion amenable to injection, biopsy, and RECIST
assessment, the lesion must be =2 centimeters (cm)
- Biopsy Cohort Enrichment: Participants must have a tumor lesion amenable to
biopsy and consent to a pre-treatment and an on-treatment biopsy
- All lesion(s) targeted for the initial injection must be =0.5 cm on longest diameter,
be at least 5 mm thick, and have distinct borders based on exam or imaging, not close
to critical structures such as major vessels, nerves, or airways
- Participants must have measurable disease as determined by RECIST v1.1 (solid tumors)
or Cheson 2014 criteria (lymphomas).
- Dose Expansion: Participants must have at least 1 measurable lesion per RECIST v1.1
which has not been previously irradiated
- Eastern Cooperative Oncology Group (ECOG) performance status of =1
- Adequate hematological and biological function
- Adequate thyroid function: Thyroid-stimulating hormone within normal range.
- Female participants of childbearing potential must have a negative serum pregnancy
test during screening.
- Male and female participants must agree to use a highly reliable method of birth
control.
- Must have life expectancy of at least 12 weeks
- Body weight >30 kilograms (kg)
Exclusion Criteria:
- Active central nervous system tumors or metastases
- Treatment with chemotherapy, radiation (local radiation for palliative care is
permitted), hormonal anti-cancer treatment, or biologic therapy <14 days prior to the
first day of study treatment (Cycle 1 Day 1 [C1D1]). Treatment with any other
investigational agent or treatment with any anti-cancer monoclonal antibody,
immunostimulant, or vaccine <28 days prior to C1D1
- Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria
- Participants with Grade =2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician
- Participants with irreversible toxicity not reasonably expected to be exacerbated
by the treatment with durvalumab may be included only after consultation with the
Study Physician
- Has active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [for example, colitis or Crohn's disease], diverticulitis
[with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [for example, granulomatosis with polyangiitis, Graves'
disease, rheumatoid arthritis, hypophysitis, uveitis]). The following are exceptions
to this criterion:
- Participants with vitiligo or alopecia
- Participants with hypothyroidism (for example, following Hashimoto syndrome)
stable on hormone replacement
- Participants with any chronic skin condition that does not require systemic
therapy
- Participants without active disease in the last 5 years may be included but only
after consultation with the Moderna medical monitor
- Participants with celiac disease controlled by diet alone
- Has a history of primary immunodeficiency, allogenic solid organ transplantation, or
tuberculosis
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study
treatment. Note: Participants, if enrolled, should not receive live vaccine whilst
receiving study treatment and up to 30 days after the last dose of study treatment.
- History of human immunodeficiency virus infection
- Active/chronic hepatitis B or C
- Any of the following cardiac abnormalities:
- Medically uncontrolled hypertension
- New York Heart Association Class III or IV cardiac disease
- Myocardial infarction within prior 6 months
- Unstable angina
- Unstable arrhythmias or mean QT interval corrected for heart rate using
Fridericia's formula (QTcF) =470 milliseconds (ms) calculated from 3
electrocardiograms (ECGs) (within 15 minutes at 5 minutes apart)
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated carcinoma in situ without evidence of disease
- Females who are pregnant or breastfeeding
- Any other unstable or clinically significant concurrent medical condition (for
example, substance abuse, psychiatric illness/social situations, uncontrolled
intercurrent illness including active infection, arterial thrombosis, symptomatic
pulmonary embolism, active interstitial lung disease, serious chronic gastrointestinal
conditions associated with diarrhea) that would, in the opinion of the investigator,
jeopardize the safety of a participant, impact their expected survival through the end
of the study participation, and/or impact their ability to give written informed
consent or comply with the protocol
- For participants who have received prior anti-programmed death 1 (PD-1) or
anti-programmed death ligand 1 (PD-L1) therapy, a participant must not have
experienced any of the following:
- Must not have experienced a toxicity that led to permanent discontinuation of
prior immunotherapy.
- All AEs while receiving prior immunotherapy must have completely resolved or
resolved to baseline prior to screening for this study.
- Must not have experienced a Grade =3 immune related AE or an immune related neurologic
or ocular AE of any grade while receiving prior immunotherapy. Note: Participants with
endocrine AEs of Grade =2 are permitted to enroll if they are stable while maintained
on appropriate replacement therapy and are asymptomatic.
- Must not have required the use of additional immunosuppression other than
corticosteroids for the management of an AE, not have experienced recurrence of an AE
if re-challenged, and not currently require maintenance doses of >10 milligrams (mg)
prednisone or equivalent per day.
- Has an active infection including tuberculosis (clinical evaluation that includes
clinical history, physical examination and radiographic findings, and tuberculosis
testing in line with local practice), hepatitis B (known positive HBV surface antigen
[HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2
antibodies). Participants with a past or resolved HBV infection (defined as the
presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
Participants positive for hepatitis C (HCV) antibody are eligible only if polymerase
chain reaction is negative for HCV RNA.
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
- Has a history of leptomeningeal carcinomatosis.
- Has involvement in the planning and/or conduct of the study.
- Must not plan to donate blood or blood components while participating in this study
and through 90 days after the last dose of study treatment
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