Phase 2 study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3?) inhibitor, plus platinum chemotherapy with or without immunotherapy in patients with advanced, metastatic Salivary Gland Carcinoma

This trial is investigating an intravenous (IV) medication called 9-ING-41 in combination
with chemotherapy (carboplatin) for the treatment of advanced salivary gland cancers.

The names of the study drug(s) involved in this study are:

- 9-ING-41 (a GSK-3β inhibitor)

- Carboplatin chemotherapy

Inclusion Criteria:

- Participants must have histologically confirmed salivary gland carcinoma (any
histologic subtype, including ACC) with evidence of recurrent, metastatic or advanced,
unresectable disease.

- Willing to provide tumor tissue from a diagnostic biopsy or prior surgery.

- Age 18 years or older

- ECOG performance status 0-2 (see Appendix A)

- Participant must have organ and marrow function as defined below within 14 days prior
to study registration:

- leukocytes ≥ 3,000/mcL

- absolute neutrophil count ≥ 500/mcL

- hemoglobin ≥ 8.5 g/dL

- platelets ≥ 75,000/mcL

- total bilirubin ≤ 2.0 g/dL

- AST(SGOT)/ALT(SGPT) ≤ 2.5× institutional upper limit of normal

- creatinine within normal institutional limits OR

- creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal

- Participants must have documentation of a new or progressive lesion on a radiologic
imaging study performed within 12 months prior to study registration (progression of
disease over any interval is allowed) and/or new or worsening disease-related symptoms
within 12 months prior to study registration. This assessment is performed by the
treating investigator. Evidence of progression by RECIST v1.1 criteria not required.

- Participants must have at least one RECIST v1.1 measurable non-CNS based lesion, as
defined as at least one lesion that can be accurately measured in at least one
dimension (longest diameter to be recorded for non-nodal lesions and short axis for
nodal lesions) ≥ 1 cm with CT scans or MR imaging.

- Prior systemic therapy: At least 2 weeks must have elapsed since the end of prior
chemotherapy, biological agents (3 weeks for anti-cancer monoclonal antibody
containing regimens) or any investigational drug product, with adequate recovery of
treatment-related toxicity to NCI CTCAE Version 5.0 grade ≤1 (or tolerable grade 2) or
back to baseline (except for alopecia or neuropathy). Any number of prior therapies
for recurrent/metastatic SGC are permitted (including prior carboplatin exposure); but
prior therapy for recurrent/metastatic SGC is not required for participation.

- Ability to understand and the willingness to sign a written informed consent document.

Female subjects of childbearing potential should have a negative urine or serum pregnancy
test within 14 days of study registration. Female subjects of childbearing potential should
have a negative urine or serum pregnancy test repeated within 72 hours prior to receiving
the first dose of study medication. WOCBP will be instructed to adhere to contraception for
a period of 90 days after the last dose of investigational product. "Women of childbearing
potential (WOCBP)" is defined as any female who has experienced menarche and who has not
undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not
postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over
45 in the absence of other biological or physiological causes. In addition, women under the
age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater
than 40 mIU/mL.

- Men who are sexually active with WOCBP must agree to use any contraceptive method with
a failure rate of less than 1% per year. Men who are sexually active with WOCBP will
be instructed to adhere to contraception for a period of 90 days after the last dose
of investigational product. Women who are not of childbearing potential (i.e., who are
postmenopausal or surgically sterile as well as azoospermic men) do not require
contraception. See Appendix B for further guidance on contraception.

Exclusion Criteria:

- Metastatic disease impinging on the spinal cord or threatening spinal cord
compression. Patients that have had previous treatment of disease with impinging on
the cord with either surgery or radiotherapy with clinical or radiographic evidence of
response or stability are eligible.

- Participant has known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases may
participate provided they are stable (without evidence of progression by imaging for
at least four weeks prior to the first dose of trial treatment), and have no evidence
of new or enlarging brain metastases.

- Concurrent administration of other cancer specific therapy or investigational agents
during the course of this study is not allowed.

- Patients on anticoagulants that require INR monitoring (such as warfarin).

- Uncontrolled intercurrent illness including but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia.

- Pregnant or lactating women.

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include: basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer, and
low-risk prostate adenocarcinoma being managed with active surveillance. A history of
another separate malignancy in remission without evidence of active disease in the
last 2 ears is permitted.