A Study of NX-1607 in Adults With Advanced Malignancies

Key Inclusion Criteria:

• Age ≥ 18 years.

• Measurable disease per disease-specific response criteria.

• Patients must have disease that is metastatic or unresectable and have receivedstandard treatment options, are not candidates for standard treatment options, orwill otherwise be prevented from receiving any standard treatment options.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Minimum of 3 weeks or 5 half-lives (whichever is shorter) since last dose ofsystemic cancer therapy (unless otherwise specified) or minimum of 2 weeks sincelast radiotherapy, or minimum of 6 weeks since last systemic therapy withnitrosoureas, antibody-drug conjugate, or radio immuno-conjugate therapy.

• Adequate organ and bone marrow function, in the absence of growth factors (withlimited exception for DLBCL), as defined by laboratory parameters.

• Patients of child-bearing potential must use adequate contraceptive measures toavoid pregnancy for the duration of the study as defined in the protocol.

• Patient must be willing and able to adhere to the prohibitions and restrictionsspecified in the protocol.

• Each patient must sign an informed consent form (ICF).

• Histological or cytological diagnosis of platinum-resistant EOC, including primaryperitoneal and fallopian tube carcinoma; gastric/GEJ cancer; HNSCC; recurrent andeither metastatic or unresectable melanoma; NSCLC; mCRPC; MPM; TNBC; locallyadvanced or metastatic urothelial cancer; cervical cancer; MSS CRC; or DLBCL (including DLBCL-RT)

• Accessible tumor (for all cohorts) or lymph node (DLBCL only) for biopsy (Phase 1bonly).

Key Exclusion Criteria:

• Active untreated brain metastases.

• Patient has any of the following:

• Uncontrolled intercurrent illness including, but not limited to, poorly controlledhypertension or diabetes, or ongoing active infection requiring systemic therapy.

• Patients with primary refractory EOC defined as patients who do not respond to theirfirst platinum-containing regimen or who relapse less than 6 months after completionof that first platinum-containing regimen

• Psychiatric illness that would limit compliance with study requirements.

• Treatment with any of the following prior to the first dose of NX-1607: CPI (anti-PD-1, PD-L1, cytotoxic T-lymphocyte-associated protein 4, etc) within 3 weeks;autologous or allogeneic stem cell transplant within 100 days; prior systemic cancertherapy within 3 weeks or 5 half-lives (whichever is shorter) (unless otherwisespecified) (including hormonal therapy except for hormonal prophylaxis for a priormalignancy); prior radiotherapy within 2 weeks; prior systemic therapy withnitrosoureas, antibody-drug conjugate, or radio-immuno-conjugate therapy within 6weeks; use of strong or moderate CYP3A4 inducers or inhibitors within 14 days or 7days, respectively, or 5 half-lives (whichever is longer)

• History of CAR-T therapy within 30 days prior to the first dose of NX-1607.

• Toxicities from previous anti-cancer therapies that have not resolved to baselinelevels or to Grade 1 or less except for Grade 2 alopecia and Grade 2 peripheralneuropathy or patients receiving endocrine replacement therapy

• Patients who experienced Grade 3 or higher irAEs with prior immunotherapy.

• History of uveitis, or an active autoimmune disease that has required systemictreatment in the past 2 years (i.e., with use of disease modifying agents,corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine,insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) is not considered a form of systemic treatment and is allowed.

• Unable to swallow capsules or has malabsorption syndrome, disease significantlyaffecting gastrointestinal function, or resection of the stomach or small bowel orulcerative colitis, symptomatic inflammatory bowel disease, or partial or completebowel obstruction likely to interfere with the delivery, absorption, or metabolismof NX-1607.

• Known allergies, hypersensitivity, or intolerance to components of NX-1607.

• Pregnant, breastfeeding, or planning to become pregnant while enrolled in this studyor within 6 months after the last dose of NX-1607.

• Patient is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of NX-1607 and, as applicable, within 6 months afterthe last dose of paclitaxel.

• Patient has had major surgery (e.g., requiring general anesthesia) within 4 weeksbefore the planned first dose of NX-1607, or will not have fully recovered fromsurgery, or has surgery planned during the time the patient is expected toparticipate in the study or within 4 weeks after the last dose of NX-1607. Note:Patients with minor planned surgical procedures to be conducted under localanesthesia may participate.

• Vaccinated with a live vaccine within 28 days (with the exception of the annualinactivated influenza vaccine) or COVID-19 vaccination within 14 days prior to thefirst dose of NX-1607.

• Active known second malignancy with the exception of any of the following:

• Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin,or in situ cervical cancer.

• Adequately treated Stage I cancer from which the patient is currently inremission and has been in remission for ≥ 2 years.

• Low-risk prostate cancer with Gleason score < 7 and PSA < 10 ng/mL.

• Any other cancer from which the patient has been disease-free for ≥ 2 years.

• Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Patientswith well controlled HIV (e.g., CD4 > 350/mm3 and undetectable viral load) areeligible.

• Current active hepatitis, including hepatitis A (hepatitis A virus immunoglobulin M [IgM] positive), hepatitis B (hepatitis B virus [HBV] surface antigen positive), orhepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV RNA).Patients with HCV with undetectable virus after treatment are eligible. Patientswith prior exposure to HBV may be entered if quantitative PCR is negative.

• Use of systemic corticosteroids (> 20 mg prednisone or equivalent) within 15 days (except for prophylaxis for radio diagnostic contrast reactions and/or prophylaxisfor patients receiving paclitaxel), or other immunosuppressive drugs within 30 days,prior to the first dose of NX-1607.

• Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than thedaily adequate intake of 30 µg [NIH 2020] (Note: Patients who switch from a highdose to a dose of 30 µg/day or less at least 1 day prior to Screening assessmentsare eligible for study entry).

• Receipt of an IP or has been treated with an investigational device within 3 weeksor 5 half-lives (whichever is shorter) prior to the first dose of NX-1607.

• Any of the following within 6 months prior to the first dose of NX-1607 or ongoing:

• Myocardial infarction

• Unstable angina

• Unstable symptomatic ischemic heart disease

• New York Heart Association Class III or IV heart failure

• Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, orsymptomatic cerebrovascular events)

• Any other significant cardiac condition (e.g., pericardial effusion,restrictive cardiomyopathy, severe untreated valvular stenosis, or severecongenital heart disease)

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with theparticipant's participation for the full duration of the study, or is not inthe best interest of the participant to participate, in the opinion of thetreating Investigator in consultation with the Medical Monitor.