A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors

Summary

Objectives

Inclusion Criteria:

- Must have a pathologically confirmed, advanced and unresectable or metastatic solid
tumor listed below with documented disease progression on last standard treatment.

For Part 1 only: Patients must be refractory to, or intolerant of existing therapy(ies)
known to provide clinical benefit for their condition.

Part 1 Dose Escalation and Food Effect Sub-study:

1. Ovarian cancer

2. Endometrial cancer (only 'endometrioid' subtype requires CCNE1 amplification)

3. Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1
amplification

4. Small cell lung cancer (SCLC)

5. Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone
receptor negative)

6. HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer
(must have progressed following treatment with a CDK4/6 inhibitor, and is not
suitable for endocrine therapy [ET])

7. Other solid tumors with CCNE1 amplification

Part 2 Dose Expansion:

Part 2A: HR+ and HER2- breast cancer that is locally advanced and unresectable (Stage
III) or metastatic (Stage IV); previously treated with =1 line of SOC including CDK4/6
inhibitor plus ET and not suitable for further ET. Subjects must have progressed after
receiving therapy for =3 months in the metastatic setting or for =6 months in the
adjuvant setting. Subjects must have received =2 lines of systemic cytotoxic therapy
(chemotherapy or cytotoxic antibody drug conjugate) in the metastatic setting.

Part 2B: Advanced platinum-based chemotherapy- resistant or refractory epithelial
ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer (defined as
recurrence =6 months after completing platinum-based regimen) with progression on at
least one platinum containing therapy and previously treated with =4 prior lines of
systemic therapy administered for advanced/metastatic disease.

Part 2C: Advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma
with progression on at least one systemic therapy and previously treated with =3 prior
lines of systemic therapy administered for advanced/metastatic disease, with CCNE1
amplification as determined by NGS by local liquid or tissue test.

Part 2D: Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma
previously treated with =4 prior lines of systemic therapy administered for
advanced/metastatic disease (only endometrioid subtype will require CCNE1 amplification
as determined by NGS by local liquid or tissue test).

Part 2E: Advanced/recurrent uterine carcinosarcoma previously treated with 1 prior
platinum-based chemotherapy regimen and =3 prior lines of systemic therapy. Prior
bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the
start of study drug.

- Measurable disease per RECIST v1.1, except for subjects with HR+/HER2- breast cancer
or endometrial cancer (Part 1) who must have measurable or evaluable (including skin
or bone lesion only) disease.

- Age =18 years

- ECOG PS 0-1

- Have adequate organ function

- Subjects with female reproductive organs must be surgically sterile,
post-menopausal, or, if of child-bearing potential, must meet pre-specified criteria

- Subjects who are capable of insemination must meet pre-specified criteria

- Ability to swallow oral medications.

- Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment
and on-treatment.

Exclusion Criteria:

- Locally advanced solid tumor that is a candidate for curative treatment through
radical surgery and/or radiotherapy, or chemotherapy.

- History of another malignancy with exceptions

- History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic
lymphohistiocytosis.

- Failed to recover from effects of prior anticancer treatment therapy to baseline or
Grade = 1 severity (per CTCAE)

- Clinically significant cardiovascular event within 6 months prior to start of
NKT3964 treatment

- Known active CNS metastases and/or carcinomatous meningitis

- Clinically active interstitial lung disease currently requiring treatment

- History of uveitis, retinopathy or other clinically significant retinal disease

- Active or chronic corneal disorders, other active ocular conditions requiring
ongoing therapy, or any clinically significant corneal disease

- Active wound healing from major surgery within 1 month or minor surgery within 10
days before the first dose of NKT3964.

- Known human immunodeficiency virus (HIV), active hepatitis B or C infection

- Prior investigative treatment with a selective or nonselective CDK2 inhibitor or
degrader

- Childs-Pugh class B or C cirrhosis or any other clinically significant liver
disorder

- Palliative radiation therapy within 14 days or other radiation therapy within 4
weeks prior to C1D1