PAK4 and NAMPT in Patients With Solid Malignancies or NHL (PANAMA)

This is a first-in-human, multi-center, open-label clinical study with separate Dose
Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of
KPT-9274, a dual inhibitor of PAK4 and NAMPT, in patients with advanced solid malignancies
(including sarcoma, colon, lung, etc.) or NHL for which all standard therapeutic options
considered useful by the investigator have been exhausted.

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible to enroll in this
study.

1. Written informed consent obtained prior to any screening procedures and in accordance
with federal, local, and institutional guidelines.

2. Age ≥ 18 years.

3. Patients with advanced solid malignancies or NHL.

4. Patients must have a site of disease amenable to biopsy and be a candidate for biopsy
according to the treating institution's guidelines.

5. Dose Escalation Phase: Patients will be enrolled according to their NAPRT1 status at a
ratio of 2:1 (NAPRT1 negative:NAPRT1 positive). The NAPRT1 status must be determined
prior to enrollment based on evaluation of a fresh tumor biopsy or archival tissue
prior to screening.

6. Life expectancy of ≥ 3 months.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not eligible to enroll in this
study.

1. Time since the last prior therapy for treatment of advanced solid malignancies or
NHL**:

1. Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including
investigational anti-cancer therapy ≤ 2 weeks prior to C1D1.

2. Palliative steroids for disease related symptoms < 7 days prior to C1D1.
**Patients must have recovered or stabilized (Grade 1 or to their baseline for
non-hematologic toxicities, ≤ Grade 2 or to their baseline for hematologic
toxicities) from toxicities related to their previous treatment except for
alopecia. In specific cases, patients with Grade 2 non-hematologic toxicities
will be allowed following approval by the Karyopharm medical monitor.

2. Major surgery within four weeks before C1D1.

3. Active infection with completion of therapeutic antibiotics, antivirals, or
antifungals within one week prior to C1D1. Prophylactic antibiotics, antivirals or
antifungals are permitted.

4. Active peptic ulcer disease or other active gastrointestinal bleeds.