Study of RXDX-105, Potent RET Inhibitor in Patients With Advanced Lung Cancer and Other Solid Tumors

• Status: Completed
• Trial end date: 2019-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a first-in-human, multicenter, open-label study consisting of 2 phases. Phase 1 is a dose escalation study of RXDX-105 (formerly known as CEP-32496) in patients with advanced solid tumors aimed at defining the recommended Phase 2 dose (RP2D) and schedule for administration. Phase 1b is a dose expansion in approximately 90 patients with advanced solid tumors with specific histologies and/or molecular alterations of interest. Patients in Phase 1b will be treated at the RP2D determined in Phase 1.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche; Ignyta, Inc.
• Treatments: Agerafenib

Criteria

Inclusion Criteria for Phase 1b:

1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory

• Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available

2. Prior Treatment:

• Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed

• NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve

• Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies

3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease

4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. The use of seizure prophylaxis is allowed. Patients requiring steroids must be at a stable or decreasing dose for at least 2 weeks prior to the start of RXDX-105 treatment.

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

6. Able to ingest oral medication

7. Other inclusion criteria apply

Exclusion Criteria for Phase 1b:

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 (4 weeks for antibody therapy and immunotherapy, and 2 weeks for bevacizumab in colon cancer patients)

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

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. History of non-pharmacologically induced prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 500 milliseconds from ECGs performed at least 24 hours apart)

5. Major active infection requiring parenteral antibiotics

6. 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

7. History of other previous cancer that would interfere with the determination of safety or efficacy of RXDX-105 with respect to the qualifying solid tumor malignancy

8. Known infection with human immunodeficiency virus (HIV) and active hepatitis B or hepatitis C

9. Current participation in another clinical study of an investigational agent, vaccine, or device. Concomitant participation in observational studies is acceptable

10. Presence of a significant gastrointestinal disorder that, in the opinion of the Investigator or Sponsor, could interfere with absorption of RXDX-105 (e.g., malabsorption syndrome, gastrointestinal surgery)

11. Known hypersensitivity to any of the components of RXDX-105