Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors



Status:Terminated
Conditions:Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:9/19/2018
Start Date:February 15, 2018
End Date:June 5, 2018

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A Study of RXDX-106, an Oral Immunomodulatory TYRO3, AXL, and MER (TAM) Tyrosine Kinase Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors

This is a first-in-human, open label, multicenter, dose escalation study of RXDX-106 in
patients with locally advanced or metastatic solid tumors, who have no available therapy
likely to convey clinical benefit.

This study will examine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and
preliminary efficacy of RXDX 106.

The primary objective of Phase 1 is to assess safety and tolerability, determine the
recommended phase 2 dose (RP2D) and assess the pharmacokinetics of RXDX-106. The secondary
objective is to evaluate the preliminary antitumor activity of RXDX-106, as assessed by
objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1
(RECIST v1.1) and Immune Response Related Criteria in Solid Tumors (iRECIST) in patients with
advanced or metastatic solid tumors.

The proposed starting dose of RXDX-106 was calculated based upon nonclinical toxicology
studies to determine a recommended first-in-human starting dose, which may be below the
biologically active level. Therefore, in order to minimize the number of patients treated at
this dose, an accelerated titration design will be used for the first cohort, after which, a
conventional 3+3 scheme will be followed for enrollment in subsequent dose levels.

Final determination of the single agent RP2D will be based on available safety, tolerability,
PK, pharmacodynamics, and efficacy data from different dose levels and schedules tested, but
will be no higher than the maximum tolerated dose. After RP2D has been determined, additional
expansion cohorts of patients (up to 15) with specific tumor types, treatment history, and/or
expression of a specific biomarker may be enrolled.

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed diagnosis of locally advanced
or metastatic solid tumor disease for which standard therapy is not effective,
available, acceptable, or is intolerable.

2. Dose level 2 (20 mg) and higher: willing to provide baseline and on treatment tumor
biopsies (3 weeks after RXDX-106 treatment initiation), provided the procedure is
clinically feasible and not deemed unsafe by the investigator.

3. Prior anticancer therapy is allowed, including prior checkpoint inhibitor treatment.

4. Must have measurable disease per RECIST 1.1 as assessed by computed tomography (CT)
scan or magnetic resonance imaging (MRI).

a. Lesion/s deemed accessible to biopsy for both before and on-treatment biopsies.

5. Males or females aged ≥18 years at screening.

6. Screening laboratory values:

1. Hemoglobin ≥9 g/dL

2. Absolute neutrophil count ≥1500 cells/mm3

3. Platelet count ≥100,000 cells/mm3

4. Total bilirubin ≤1.5 × upper limit of normal (ULN)

5. Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN

6. Serum creatinine ≤1.5 mg/dL or estimated glomerular filtration rate (eGFR) ≥60
mL/min/1.73 m2

7. International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5 × ULN (unless
patient is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants)

8. Activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless patient is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants)

9. TSH within normal limits at baseline, (if not WLN, then total T3 or free T3 and
free T4 should be within normal limits) or stable with treatment.

7. Patients with treated stable CNS metastases that are asymptomatic (including
leptomeningeal carcinomatosis) are allowed, if there is no evidence of progression for
at least 4 weeks after CNS-directed treatment as ascertained by clinical examination
and brain imaging. Patients requiring steroids must be at a stable or decreasing dose
(≤10 mg/day dexamethasone or equivalent) for at least 2 weeks prior to the start of
treatment. The use of seizure prophylaxis is allowed.

8. Resolution of any clinically significant toxic effects of prior therapy to grade 0 or
1 according to the National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI CTCAE), Version 4.03 (exception of alopecia and grade 2 peripheral
neuropathy).

9. Eastern Cooperative Oncology Group (ECOG) performance status of <2.

10. Other inclusion criteria apply.

Exclusion Criteria:

1. Treated with systemic anticancer therapy or an investigational agent within 2 weeks or
5 half-lives, whichever is shorter, prior to start of study drug treatment. Washout
will be 2 weeks for antibody therapy and immunotherapy.

2. Major surgery 21 days or less prior to starting study drug or has not recovered from
adverse effects from such procedure.

3. Radiotherapy within 2 weeks prior to start of study drug treatment (palliative
radiation or stereotactic radiosurgery within 7 days prior to start of study
treatment). Patients must have recovered from all radiotherapy-related toxicities.

4. Has received a live-virus vaccination within 30 days prior to start of study drug
treatment.

a. Seasonal flu and other inactivated vaccines that do not contain live virus are
permitted.

5. Severe or unstable medical condition, such as congestive heart failure (New York Heart
Association [NYHA] Class III or IV), ischemic heart disease, uncontrolled
hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an
uncontrolled cardiac arrhythmia requiring medication (≥grade 2, according to NCI CTCAE
v4.03), myocardial infarction within 6 months prior to starting study treatment, or
any other significant or unstable concurrent medical illness that in the opinion of
the investigator would preclude protocol therapy.

6. History of non-pharmacologically induced prolonged QTc interval >480 milliseconds.

7. History of other previous or concurrent cancer that would interfere with the
determination of safety or efficacy assessment of RXDX-106 with respect to the
qualifying solid tumor malignancy.

8. Major active infection requiring parenteral antibiotics.

9. Known HIV infection or active infection with hepatitis B or C. Patients with unknown
status at the time of enrollment must be tested during screening.

10. Unable to swallow oral medication.

11. Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut
syndrome) or other malabsorption syndromes that would reasonably impact drug
absorption.

12. Active autoimmune disease requiring immunosuppressive treatment or history of
autoimmune disease requiring immunosuppressive therapy (e.g. requirement for systemic
therapy with >10 mg/day prednisone-equivalent) or any other concurrent use of
immunosuppressive therapy.

13. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.

14. Active retinal pigment epithelium (RPE)/photoreceptor disorders such as; retinitis
pigmentosa, cone-rod dystrophies, Bests dystrophy, Stargardt disease (STGD), macular
degeneration.

15. Current participation in another clinical study of an investigational agent, vaccine,
or device. Concomitant participation in observational studies is acceptable after
sponsor approval.
We found this trial at
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San Antonio, Texas 78229
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San Antonio, TX
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