A Phase Ib Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) of Avelumab in Combination With M9241(NHS-IL12) (JAVELIN IL-12)

Inclusion Criteria:

Part A:

- Subjects must have signed written informed consent.

- Male or female subjects age greater than equals to (>=)18 years.

- Subjects must have histologically or cytologically proven metastatic or locally
advanced solid tumors for which no standard therapy exists, standard therapy has
failed, subject is intolerant of established therapy known to provide clinical benefit
for their condition, or standard therapy is not acceptable to the subject.

- Subjects who have been treated previously with a checkpoint inhibitor may enroll
(except as outlined below for expansion cohorts).

- At least 1 unidimensional radiographically measurable lesion based on Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), except for subjects
with metastatic castration-resistant prostate cancer (CRPC) or metastatic breast
cancer who may be enrolled with objective evidence of disease without a measureable
lesion.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at Screening

- Estimated life expectancy of more than 12 weeks

- Adequate hematological function as defined below:

- White blood cells (WBC) count >= 3.0 × 10^9 per liter (/L)

- Absolute neutrophil count >= 1.5 × 10^9/L

- Lymphocyte count >= 0.5 × 10^9/L

- Platelet count >= 100 × 10^9/L

- Hemoglobin >= 9 gram per deciliter (g/dL) (may have been transfused)

- Adequate hepatic function as defined below:

- A total bilirubin level lass than equals to (<=) 1.5 × the upper limit of normal
(ULN) range • Aspartate aminotransferase (AST) levels <= 2.5 × ULN (≤ 3 × ULN for
expansion cohorts)

- Alanine aminotransferase (ALT) levels <= 2.5 × ULN (≤ 3 × ULN for expansion
cohorts)

- Subjects with documented Gilbert disease are allowed if total bilirubin > 1.5 but
less than 3 × ULN

- Adequate renal function as defined by an estimated creatinine clearance >= 50
milliliter per minute (mL/min) according to the Cockcroft-Gault formula

- Negative blood pregnancy test at Screening for women of childbearing potential. For
the purposes of this trial, women of childbearing potential are defined as all female
subjects after puberty unless they are postmenopausal for at least 1 year, are
surgically sterile or are sexually inactive.

- Highly effective contraception (ie, methods with a failure rate of less than 1% per
year) must be used before the start of treatment, for the duration of the trial
treatment, and for at least 50 days after stopping study treatment for both men and
women if the risk of conception exists. The effects of avelumab and NHS-IL12 on the
developing human fetus are unknown; thus, women of childbearing potential and men must
agree to use highly effective contraception.

Part B:

- Urothelial carcinoma (UC) post-platinum: Histologically or cytologically confirmed
locally advanced or metastatic transitional cell carcinoma of the urothelium
(including renal pelvis, ureters, urinary bladder, and urethra). Subjects must have
progressed after treatment with at least 1 platinum containing regimen for inoperable
locally advanced or metastatic UC or disease recurrence. Availability of either tumor
archival material (< 6 months old)or fresh biopsies (obtained within 28 days) is
acceptable with one of these being mandatory. For formalin-fixed paraffin-embedded
samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor
archival material must be suitable for biomarker assessment.

- Non-small cell lung cancer (NSCLC), first-line metastatic: Stage IV (per seventh
International Association for the Study of Lung Cancer classification) histologically
confirmed NSCLC. Subjects must not have received treatment for their metastatic
disease. Subjects could have received adjuvant chemotherapy or loco-regional treatment
that included chemotherapy for locally advanced disease, as long as disease recurrence
occurred at least 6 months after the completion of the last administration of
chemotherapy. Only epidermal growth factor receptor (EGFR) and anaplastic lymphoma
kinase (ALK) wild-type are allowed (ie, EGFR mutation and ALK translocation / re
arrangement excluded). Non squamous cell histologies and never / former light smoker
(< 15 pack years) squamous cell carcinoma subjects (per local standard of care)
require testing if status is unknown. Subjects must have low tumor PD-L1 expression
defined as < 50% tumor proportion score determined using PD-L1 IHC 22C3 pharmDx test
or an equivalent Food and Drug Administration (FDA)- approved PD-L1 test. Availability
of either tumor archival material or fresh biopsies within 28 days is acceptable with
one of these being mandatory. For FFPE samples, either block or sections (> 15) may be
provided. Tumor biopsies and tumor archival material must be suitable for biomarker
assessment. This cohort will not be opened for enrollment in Belgium, Czech Republic,
Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom.

- Colorectal cancer (CRC): Histologically or cytologically confirmed recurrent or
refractory metastatic CRC (according to American Joint Committee on Cancer /
International Union Against Cancer Tumor Node Metastasis [TNM] Staging System seventh
edition) after failure of prior therapy containing oxaliplatin / fluoropyrimidine and
/ or irinotecan / fluoropyrimidine and, if eligible, cetuximab (Erbitux®) and
bevacizumab (Avastin®). Only subjects with microsatellite instability (MSI)-low or
microsatellite stable (MSS) metastatic CRC are eligible. Subjects without existing MSI
test results will have MSI status performed locally by a Clinical Laboratory
Improvement Amendments (CLIA)-certified IHC or polymerase chain reaction (PCR)-based
test (PCR based MSI test is preferred). Subjects must be willing to undergo an
on-treatment biopsy procedure. Availability of either tumor archival material or fresh
biopsies within 28 days is acceptable with one of these being mandatory. For FFPE
samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor
archival material must be suitable for biomarker assessment. For Belgium, Czech
Republic, Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom, subjects in
the second-line setting should have exhausted or be considered ineligible or
intolerant (in the opinion of the Investigator) of available second-line chemotherapy
options.

- Renal cell carcinoma (RCC), primary immune checkpoint inhibitor failure:
Histologically or cytologically documented metastatic RCC with a component of clear
cell subtype. Subjects must have had progressive disease (PD) within 6 months or best
overall response of stable disease (SD) for ≥ 6 months following start of therapy with
any antibody / drug targeting T cell co-regulatory proteins (immune checkpoints) such
as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) for
advanced or metastatic disease (either as monotherapy or combination therapy, in any
line). Availability of a fresh tumor biopsy is mandatory for eligibility in the RCC
cohort. The biopsy or surgical specimen should be collected within 28 days prior to
the first IMP administration. Subjects must also be willing to undergo an on-treatment
biopsy procedure.

Exclusion Criteria:

- Concurrent treatment with a non-permitted drug/intervention (listed below)

- Anticancer treatment (eg, cytoreductive therapy, radiotherapy, immune therapy,
cytokine therapy, monoclonal antibody, targeted small molecule therapy) or any
investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior
to start of trial treatment, or not recovered from adverse event (AE) related to
such therapies, with the following exceptions: Palliative radiotherapy delivered
in a normal organ-sparing technique is permitted; Erythropoietin and
darbepoetin-α are permitted; Hormonal therapies acting on the
hypothalamic-pituitary-gonadal axis are permitted (i.e. luteinizing
hormone-releasing hormone agonist/antagonists). No other hormonal anticancer
therapy is permitted.

- Major surgery (as deemed by Investigator) for any reason, except diagnostic
biopsy, within 4 weeks prior to start of trial treatment, or not fully recovered
from surgery within 4 weeks prior to start of trial treatment

- Subjects receiving immunosuppressive agents (such as steroids) for any reason
should be tapered off these drugs before start of trial treatment, with the
following exceptions: Subjects with adrenal insufficiency, may continue
corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone
daily; Administration of steroids through a route known to result in a minimal
systemic exposure (topical, intranasal, intra-ocular, or inhalation) is
permitted; Previous or ongoing administration of systemic steroids for the
management of an acute allergic phenomenon is acceptable as long as it is
anticipated that the administration of steroids will be completed in 14 days, or
that the dose after 14 days will be equivalent to <= 10 mg prednisone daily.

- Any prior treatment with any form of interlukin-12 (IL-12)

- For the NSCLC, CRC, and UC expansion cohorts, prior therapy with any antibody / drug
targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1,
anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) antibody is prohibited.

- Intolerance to checkpoint inhibitor therapy, as defined by the occurrence of an AE
requiring drug discontinuation.

- Active or history of primary or metastatic central nervous system tumors

- Prior organ transplantation, including allogeneic stem-cell transplantation

- Previous malignant disease (other than the indication for this trial) within the last
5 years (except adequately treated non-melanoma skin cancers, carcinoma in situ of
skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission
without further recurrence was achieved at least 2 years prior to trial entry and the
subject was deemed to have been cured with no additional therapy required or
anticipated to be required.

- Significant acute or chronic infections requiring systemic therapy including, among
others:

- History of testing positive test for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome

- Hepatitis B or C infection (HBV surface antigen positive and HBV core antibody
positive with reflex to positive HBV deoxy ribonucleic acid (DNA) or HBV core
antibody positive alone with reflex to positive HBV DNA or positive hepatitis C
virus [HCV] antibody with reflex to positive HCV ribonucleic acid [RNA]).
Subjects with history of infection must have polymerase chain reaction
documentation that infection is cleared.

- Active or history of autoimmune disease that might deteriorate when receiving an
immuno-stimulatory agent. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or
hyperthyroid disease not requiring immunosuppressive treatment are eligible if they
are stable on other medical treatment and do not fulfill exclusion criterion including
Uncontrolled intercurrent illness

- Known severe hypersensitivity reactions to monoclonal antibodies (Grade>= 3 National
Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03, or
uncontrolled asthma (ie, 3 or more features of partially controlled asthma)

- History of allergic reaction to methotrexate (trace methotrexate may be present in
NHS-IL12 as a part of the manufacturing process) or history of severe hypersensitivity
reaction to any other ingredient of the study drug(s) and / or their excipients. Since
NHS-IL12 contains sucrose as an excipient, subjects suffering from hereditary fructose
intolerance are also excluded

- Persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v4.03 with the
following exceptions:

- Neuropathy Grade <= 2 is acceptable.

- All grades of alopecia are acceptable.

- Endocrine dysfunction on replacement therapy is acceptable.

- Pregnancy or lactation

- Known alcohol or drug abuse as deemed by the Investigator

- Uncontrolled intercurrent illness including, but not limited to:

- Hypertension uncontrolled by standard therapies (not stabilized to 150/90
millimeter of mercury (mm Hg) or lower)

- Uncontrolled active infection

- Uncontrolled diabetes (eg, glycosylated hemoglobin [HgbA1c] >= 8%)

- Clinically significant (or active) cardiovascular disease: cerebral vascular
accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
prior to enrollment), unstable angina, congestive heart failure (New York Heart
Association Classification Class >= II), or serious cardiac arrhythmia requiring
medication

- All other significant diseases (eg, inflammatory bowel disease, current severe acute
or chronic colitis) or chronic medical conditions (including laboratory abnormalities)
that in the opinion of the Investigator might impair the subject's tolerance of trial
treatment or interpretation of trial results.

- Any psychiatric condition that would prohibit the understanding or rendering of
informed consent or that would limit compliance with trial requirements.

- Legal incapacity or limited legal capacity.

- Administration of a live vaccine within 30 days prior to trial entry.

- Any subject with possible area of ongoing necrosis (non-disease related), such as
active ulcer, non-healing wound, or intercurrent bone fracture that may be at risk of
delayed healing due to protocol therapy.

- Oxygen saturation < 90% at rest, known pulmonary fibrosis, or active interstitial lung
disease.

- History of congenital or active immunodeficiency, with the exception of acquired
treatment-related hypogammaglobulinemia requiring periodic IV immunoglobulin infusion.