CBT-101 Study for Advanced Solid Tumors and c-Met Dysregulation

• Sponsor: CBT Pharmaceuticals, Inc.
• Information provided by (Responsible Party): CBT Pharmaceuticals, Inc.

Study Description

Brief Summary:

The purpose of this study is to determine the safety, tolerability, and recommended dose of CBT-101 in individuals with advanced solid tumors and c-MET dysregulation.

Condition or disease	Intervention/treatment	Phase
Solid Tumor; Advanced Cancer; Renal Cancer; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma	Drug: CBT-101 Oral Capsules	Phase 1

Detailed Description:

This is a Phase 1, multi-center, open-label, 2-part study with a Dose Escalation Segment and Dose and Disease Expansion Cohorts study of CBT-101, a c-MET inhibitor, to determine the recommended Phase 2 dose (RP2D) and dose limiting toxicities for CBT-101, and to obtain preliminary efficacy and target engagement data, in subjects with advanced malignancies and c-Met dysregulation.

c-MET dysregulation will be determined from historical results by molecular pre-screening evaluations to determine eligibility of enrollment for both the Dose Escalation Segment and Dose and Disease Expansion Cohorts. However, in the Dose and Disease Expansion Cohorts, the c-MET historical results will be confirmed by a central laboratory retrospectively, but will not be a determinant for study entry.

Dose escalation will occur in three subject cohorts until a protocol defined dose limited toxicity (DLT) occurs and a tentative maximum tolerated dose (MTD) is determined.

At the tentative MTD or RP2D, at least 16 additional subjects for each stated tumor type (renal cell carcinoma, advanced gastric carcinoma (including gastroesophageal junction adenocarcinoma), and a biomarker driven basket of tumors with c-MET dysregulation will be assessed to further evaluate toxicity and preliminary efficacy.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	68 participants
Intervention Model:	Single Group Assignment
Intervention Model Description:	Subjects will be assigned to a dose level in the order of study entry. Treatment includes five planned dose levels (100 mg, 200 mg, 300 mg, 400 mg, 550 mg).
Masking:	None (Open Label)
Masking Description:	Open Label
Primary Purpose:	Treatment
Official Title:	Phase 1 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of CBT-101 in Subjects With Advanced Solid Tumors and c-Met Dysregulation
Actual Study Start Date :	September 27, 2017
Estimated Primary Completion Date :	June 2018
Estimated Study Completion Date :	June 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single-Arm; CBT-101Oral Capsules	Drug: CBT-101 Oral Capsules; Subjects will be assigned to a dose level of CBT-101 in the order of study entry. Treatment includes 28-day cycles at five planned dose levels (100 mg, 200 mg, 300 mg, 400 mg, 550 mg). Each treatment cycle is administered by oral capsules consecutively every 12 hours.; Other Names: PLB-1001; CBI-3103

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.03) [ Time Frame: From the time of informed consent signature to 30 days after discontinuation of study drug. ]
   Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)

Secondary Outcome Measures :

1. Determine the recommended Phase 2 dose and schedule [ Time Frame: Approximately 1 year ]
   Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)
2. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
   AUC, 0 - infinity
3. Maximum plasma concentration [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
   Cmax
4. Time to reach Cmax [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
   Tmax
5. Overall Response Rate [ Time Frame: Approximately 12 months ]
   Anti-tumor activity per RECIST v1.1
6. Duration of Response [ Time Frame: Approximately 24 months ]
   Anti-tumor activity per RECIST v1.1
7. Progression Free Survival [ Time Frame: Approximately 24 months ]
   Anti-tumor activity per RECIST v1.1

Other Outcome Measures:

1. Correlation of CBT-101 and c-MET at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
2. Correlation of CBT-101 and hepatocyte growth factor at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
3. Correlation of CBT-101 and soluble c-MET at baseline and after study treatment. [ Time Frame: Approximately 24 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Major Inclusion Criteria:

• Able to understand and comply with study procedures, understand the risks involved, and provide written informed consent.
• Dose Escalation Segment: histologically and / or cytological confirmed locally advanced, recurrent or relapsed, or metastatic incurable solid malignancy with no limit on the number of prior lines of standard therapy.

• Dose and Disease Expansion Cohorts: histologically confirmed renal cell carcinoma, gastric carcinoma (including gastro-esophageal junction adenocarcinoma), and a biomarker driven cohort of tumors with evidence of c-MET dysregulation (amplification, mutation)

  • Renal Cell Carcinoma: documented histological or cytological diagnosis of renal cell cancer with a clearcell or papillary component; progression following at least two prior lines of standard therapy including a checkpoint inhibitor and an anti-VEGFR inhibitor; archival tissue or fresh tumor biopsy
  • Gastric Carcinoma (including Gastro-Esophageal Junction Adenocarcinoma): progression following at least one prior line of standard therapy that contained a fluoropyrimidine and/or platinum and/or taxane agent; prior adjuvant or neoadjuvant therapy is counted as one regimen, provided that disease progression occurs within 6 months after the completion of adjuvant or neoadjuvant therapy; HER2 negative subjects (defined by HER2 ≤ 2+ by IHC) by medical history; archival tissue or fresh tumor biopsy

• Abnormal c-MET dysregulation, defined as the following from archival historical results of molecular pre-screening evaluations.

  • Dose Escalation Segment

    • c-MET overexpression, ≥ 50% tumor cells with immunohistochemistry Grade 3+
    • or c-MET amplification; FISH c-MET to chromosome 7 (CEP 7) ratio ≥ 2.2; NGS copy number variation ≥ 4
    • or mutation, including any deletions and any met fusions

  • Dose and Disease Expansion Cohorts

    • c-MET amplification; FISH c-MET to chromosome 7 (CEP 7) ratio ≥ 2.2; NGS copy number variation ≥ 4
    • or mutation, including any deletions and any met fusions
• Measurable disease according to RECIST v1.1
• No chemotherapy treatments within at least 3 weeks prior to first dose of study treatment. For all prior anticancer treatment, including radiotherapy or targeted agents or hormonal therapy, a duration of more than 5 half-lives of the targeted/hormonal agents used must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria.
• Adequate cardiac function (≤ NYHA Class II) or normal cardiac function with left ventricular ejection fraction (LVEF) ≥ 50% at screening.

Major Exclusion Criteria:

• Hypersensitivity to CBT-101, excipients of the drug product, or other components of the study treatment regimen.
• History of receiving treatment with any c-MET signaling pathway inhibitor (marketed or investigational agents)
• History of, or at risk for, cardiac disease (e.g., long QT syndrome [> 450 msec] or concurrent treatment with any medication that prolongs QT interval).
• Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptic and requiring high doses of steroids.
• Unable to swallow orally administered medication whole.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Systemic treatment with radionuclides within 6 weeks before randomization. Subjects with complications from prior radiation therapy are not eligible and AEs must return to baseline or ≤ Grade 1.

Contacts and Locations

Contacts

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Contact: Purvi Patel, MS	(925) 272-4090	purvi.patel@cbtpharma.com
Contact: Gavin Choy, PharmD, MBA	(925) 272-4090	gavin.choy@cbtpharma.com

Locations

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United States, Arizona
Mayo Clinic	Recruiting
Phoenix, Arizona, United States, 85054
Contact: Clinical Trial Referral Office 855-776-0015
Principal Investigator: Ramesh K Ramanathan, MD
United States, California
University of Southern California / Norris Comprehensive Cancer Center	Recruiting
Los Angeles, California, United States, 90033
Contact: Jubilee Acap 323-865-0593 jubilee.acap@med.usc.edu
Principal Investigator: Anthony El-Khoueiry, MD
United States, Florida
Mayo Clinic	Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trial Referral Office 855-776-0015
Principal Investigator: Kabir Mody, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trial Referral Office 855-776-0015
Principal Investigator: Sani H Kizilbash, MD, MPH

Sponsors and Collaborators

CBT Pharmaceuticals, Inc.

Investigators

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Study Director:	Gavin Choy, PharmD, MBA	EVP and Chief Operating Officer, CBT Pharmaceuticals, Inc.

More Information

Additional Information:

Company website for CBT Pharmaceuticals, Inc. 

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Responsible Party:	CBT Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT03175224 History of Changes
Other Study ID Numbers:	CBT-101-01
First Posted:	June 5, 2017
Last Update Posted:	December 22, 2017
Last Verified:	December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by CBT Pharmaceuticals, Inc.:

Advanced Solid Tumor; Relapsed Solid Tumor; Recurrent Solid Tumor

Additional relevant MeSH terms:

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Neoplasms; Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms	Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Urologic Neoplasms; Urogenital Neoplasms; Kidney Diseases; Urologic Diseases