A Phase 2, Open-Label Study of Amuvatinib in Combination With Platinum-Etoposide Chemotherapy in Small Cell Lung Cancer

Amuvatinib is an oral multi-targeted tyrosine kinase inhibitor which inhibits the mutant
forms of c-Kit and PDGFR alpha. It also disrupts DNA repair likely through suppression of
Homologous Recombination protein Rad51. In a Phase 1b clinical study in combination with
VP-16 and carboplatin, responses in SCLC were observed. In vitro and in vivo data
demonstrated amuvatinib synergy with VP-16 thereby further supporting this combination for
continued evaluation in clinical trials. Pharmacokinetic data from Phase 1 clinical trials
suggest that co-administration of amuvatinib did not alter exposures of standard of care
agents VP-16 or carboplatin as measured by overall exposure.

Inclusion Criteria:

1. Male or female ≥ 18 of age at the time of consent and have histologically or
cytologically confirmed SCLC

2. Measurable SCLC per RECIST guideline that meets one of the following:

- Disease progression by RECIST at anytime during platinum-etoposide (PE)
chemotherapy;

- Relapse by RECIST within 90 days after completing PE chemotherapy;

- Stable disease by RECIST as best response after at least two (2) ≥ 21-day cycles
of PE chemotherapy. The assessment of stable disease should be made at least 2
weeks after the start of the second cycle

Subjects who received another second-line therapy are eligible if they still fulfill
any one of the above three conditions, and all other eligibility criteria

3. Start treatment with the same last regimen (dose and schedule) of first-line PE
chemotherapy that they progressed or relapsed on, including any dose reductions
because of toxicity, prior to study entry

4. ECOG performance status 0 to 2

5. Adequate organ function

6. Subjects with screening 12-lead ECG with measurable QTc interval of < 450 msec. If QTc
≥ 450 msec, then confirm the reading by evaluating the mean QTc interval of triplicate
ECGs.

7. Sign approved informed consent form

Exclusion Criteria:

1. Prior exposure to amuvatinib

2. No longer eligible for first-line PE chemotherapy due to toxicity and the Investigator
believes that the risk of retreating with the same PE chemotherapy regimen would
outweigh the benefit

3. Ongoing toxicity from prior treatment unless the toxicity has resolved, or in the
opinion of the Investigator, is stable and does not compromise the safety of the
subject

4. Mixed SCLC and non-small cell lung cancer, or large cell lung cancer

5. Untreated, unstable, or symptomatic brain metastasis

6. Hypersensitivity to amuvatinib, excipients of amuvatinib, or any agent given in
association with this trial

7. A life-threatening illness, medical condition or organ system dysfunction which, in
the Investigator's opinion, could compromise the subject's safety or interfere with
study outcomes