A Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

- Histologically documented diagnosis of locally advanced or metastatic SCC (Squamous
Cell Carcinoma) of the head and neck no longer amenable to curative surgical
resection or radiation therapy.

- Refractory to platinum-based therapy (defined as disease progression within 6 months
of last dose of platinum chemotherapy)

- Patient is able swallow and absorb oral medications

- Age 18 years or older

- ECOG Performance Status (an attempt to quantify cancer patients' general well-being
and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic
and 5 is death) of 0-2

- Patients must have CT (CAT Scan) measurable disease as defined by RECIST v1.1

- Willingness and ability to comply with all study procedures

- Women of childbearing potential must have a negative serum or urine pregnancy test
within 3 days prior to treatment.

- Archival tissue available for Foundation One analysis.

- Signed and dated informed consent document indicating that the patient (or legally
acceptable representative) has been informed of all pertinent aspects of the trial
prior to enrollment.

Exclusion Criteria:

- Inability to obtain Foundation One testing on archival tissue, or, lack of previous
Next Generation Sequencing incorporating testing for NOTCH -1, -2, -3, and -4

- Impaired cardiac function including any one of the following:

- Patients with any of the following laboratory values at baseline: Absolute neutrophil
count (ANC) < 1,000/mm3 [SI units 109/L], Platelets < 75,000/mm3 [SI units 109/L],
Hemoglobin < 9.0 gm/dL [SI units gm/L], Calculated (e.g. using Cockcroft-Gault
formula) or measured creatinine clearance < 50 ml/min, Bilirubin > 1.5 x ULN, except
for patients with known Gilbert syndrome who are excluded if total bilirubin > 3.0 x
ULN or direct bilirubin > 1.5 x ULN, Aspartate transaminase (AST) > 3.0 x ULN, except
for patients with liver metastasis who are excluded if AST > 5.0 x ULN, Alanine
transaminase (ALT) > 3.0 x ULN, except for patients with liver metastasis who are
excluded if ALT > 5.0 x ULN

- Impairment of GI function or GI disease that may significantly alter the absorption
of WNT974

- Presence of ≥ CTCAE (Common Terminology Criteria for Adverse Events) Grade 2 toxicity
(except alopecia) due to prior therapy

- Malignant disease, other than that being treated in this study. Exceptions to this
exclusion criterion include the following: malignancies that were treated curatively,
and have not recurred within 3 years prior to study entry; completely resected basal
cell and squamous cell skin cancers; and completely resected carcinoma in situ of any
type

- Patients who received anti-cancer therapy prior to the first dose of WNT974 within
the following time frames: Biological therapy with a prolonged half-life (e.g.,
monoclonal antibodies) within 4 weeks, Cytotoxic agents associated with delayed
hematologic recovery (e.g., nitrosourea or mitomycin-C) within 6 weeks, Other
systemic anti-cancer agents within 3 weeks, Radiotherapy within 2 weeks

- Patients who are currently receiving treatment with medications that meet one of the
following criteria and that cannot be discontinued at least one week prior to the
start of treatment with WNT974: Strong inhibitors or inducers of CYP3A4/5, CYP3A4/5
substrates with narrow therapeutic index, known to prolong the QT interval and are
also CYP3A4/5 substrates. Refer to Appendix 1 for guidance on concomitant medication.

- Patients who have undergone any major surgery within 2 weeks prior to starting study
drug or who have not adequately recovered from previous surgery

- Active hepatitis B or C infection

- Pregnant or nursing (lactating) women

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 30 days after study treatment. Highly effective contraception
methods include: Total abstinence or, male or female sterilization, combination of
any two of the following: Use of oral, injected or implanted hormonal methods of
contraception, placement of an intrauterine device (IUD) or intrauterine system
(IUS), barrier methods of contraception. Post-menopausal women are allowed to
participate in this study.

- Sexually active males must use a condom during intercourse while taking the drug and
for 90 days after stopping treatment and should not father a child in this period.

- Other severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation

- Patients residing in prison.