A Study to Evaluate the Safety and Tolerability of ETC-1922159 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumours

NCT02521844 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: D3-002
• Study Type: interventional
• Target: 89
• Locations: 2 countries
• Sites: 11

Brief Summary

This is a Phase 1A/B study consisting of four parts.

1. 1.Part A (completed) is a non-randomised, open-label, sequential evaluation of the safety, pharmacokinetics (PK), maximum tolerated dose (MTD), and recommended dose (RD) of ETC-1922159 in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available. Dose escalation, with the goal of identifying the MTD and RD, is guided by an ordinal continual reassessment method (oCRM) model with a cohort size of one patient.
2. 2.Part A extension (completed) is a non-randomised, non-comparative, open-label evaluation of the safety and tolerability of ETC-1922159 together with the bone protective treatment (denosumab) in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available.
3. 3.Part B dose escalation (completed) is a non-randomised, open-label, sequential evaluation of the MTD, RD, safety, PK, and PD (pharmacodynamics) of ETC 1922159 in combination with pembrolizumab in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available.
4. 4.Part B dose expansion will be a non-randomised, non-comparative, open-label study evaluation of the safety and tolerability of ETC-1922159 as a single agent until disease progression and then in combination with pembrolizumab at the RD identified in the Part B dose escalation segment, in patients with advanced or metastatic, or unresectable solid malignancies that are refractory, intolerant or not suitable for available treatment according to the treating physician.

Conditions

Solid Tumors

Keywords

solid tumors; responsive to Wnt signalling regulation; RSPO fusions; Porcupine; PD-1; MSS; CRC; endometrial cancer; ovarian cancer

Outcome Measures

Primary Outcomes (9)

• Maximum Tolerated Dose (MTD) of ETC-1922159 when administered with pembrolizumab (Part B Dose Escalation)

  For 2 cycles (42 days)

• Recommended Dose (RD) of ETC-1922159 when administered with pembrolizumab (Part B Dose Escalation)

  For 2 cycles (42 days)

• Number of participants with adverse events (AEs) (Part B Dose Expansion)

  From date of enrolment until end of treatment

• Number of participants with adverse bone density imaging assessments via DEXA scan (Part B Dose Expansion)

  From date of enrolment until end of treatment

• Number of participants with abnormal 12-lead electrocardiogram (ECG) readings (Part B Dose Expansion)

  From date of enrolment until end of treatment

• Change in Eastern Cooperative Oncology Group performance status (Part B Dose Expansion)

  From date of enrolment until end of treatment

• Number of participants with abnormal clinical laboratory test results (Part B Dose Expansion)

  From date of enrolment until end of treatment

• Number of participants with abnormal vital sign measurements (Part B Dose Expansion)

  From date of enrolment until end of treatment

• Tolerability measured by monitoring of fatigue and gastrointestinal-related side effects and when applicable, immune-related side effects in patients (Part B Dose Expansion)

  From date of enrolment until end of treatment

Secondary Outcomes (13)

• Number of participants with adverse events (AEs) (Part B Dose Escalation)

  From date of enrolment until end of treatment

• Number of participants with adverse bone density imaging assessments via DEXA scan (Part B Dose Escalation)

  From date of enrolment until end of treatment

• Number of participants with abnormal 12-lead electrocardiogram (ECG) readings (Part B Dose Escalation)

  From date of enrolment until end of treatment

• Change in Eastern Cooperative Oncology Group performance status (Part B Dose Escalation)

  From date of enrolment until end of treatment

• Number of participants with abnormal clinical laboratory test results (Part B Dose Escalation)

  From date of enrolment until end of treatment

Study Arms (2)

Dose Escalation

EXPERIMENTAL

ETC-1922159 + pembrolizumab

Drug: ETC-1922159; Drug: Pembrolizumab

Dose Expansion

EXPERIMENTAL

ETC-1922159 as single agent until disease progression, then in combination with pembrolizumab at the recommended dose (RD) identified in the dose escalation segment

Drug: ETC-1922159; Drug: Pembrolizumab

Interventions

ETC-1922159 DRUG

Oral administration

Dose Escalation; Dose Expansion

Pembrolizumab DRUG

IV administration

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• + yrs (US), 21+ yrs (Singapore)
• Ability to give informed consent
• Histologically/cytologically confirmed advanced or metastatic tumors, that are unresectable solid malignancies, and that are are refractory, intolerant or not suitable to available treatment
• Objective and radiologically confirmed disease progression at screening
• Measurable disease by RECIST v1.1
• ECOG (Eastern Cooperative Oncology Group) 0-2
• Life expectancy ≥3 months
• Organ function:
• Absolute neutrophil count ≥1.0×10\^9/L
• Platelets ≥100×10\^9/L (w/o transfusions w/in 21 days)
• Hemoglobin ≥9 g/dL
• PT (prothrombin time) and PTT (partial thromboplastin time) w/in ≤1.5× ULN
• International normalised ration (INR) ≤1.5× ULN Note: If the patient is on allowed anti-coagulants the INR should be in the therapeutic range
• Total bilirubin ≤1.5× ULN
• Transaminases (AST and/or alanine aminotransferase) ≤2.5× ULN (\<5× ULN with liver metastases)

You may not qualify if:

• Male patient with sexual partner(s) of childbearing potential unwilling to use contraception. Sexually active male patients must use a condom during intercourse during the study and for 12 weeks after the end of treatment. Condom must also be used by vasectomised males.
• Female of childbearing potential, unless birth control is used during study and for 12 weeks after end of treatment.
• Pregnant or nursing (lactating) female.
• Dose Escalation: Current or anti-cancer therapy within 4 weeks pre-study or with Grade ≤1 side effects not resolved within 4 weeks pre-study.
• Dose Expansion segment: Has received previous treatment with pembrolizumab or immunotherapy treatment within 4 weeks (28 days) prior to starting the study drug is permitted
• Dose Expansion (Groups 1, 2a, 2b and 2d): Immunotherapy within 4 weeks (28 days) prior to starting study.
• Dose Expansion (Group 2c MSS endometrial cancer only): Immunotherapy either alone or in combination with lenvatinib within 4 weeks (28 days) prior starting study drug.
• Is receiving any concomitant anti-cancer therapy.
• Has used other investigational products within 4 weeks or 5 half-lives (whichever is longer) prior to first dose of study drug.
• Has evidence of other malignancy not in remission or history of other malignancy within last 3 yrs (exceptions: treated basal or skin squamous cell carcinoma or in situ cancer of cervix)
• Has central nervous system metastases, unless treated with surgery, whole brain radiation or stereotactic radiosurgery, and stable disease ≥8 weeks without steroid use for ≥4 weeks prior to first dose of study drug.
• Has received prior radiation therapy within 4 weeks, or limited field radiation within 2 weeks, prior to study drug, or with unresolved Grade ≤1 side effects.
• Has had major surgical procedure within 4 weeks of starting study drug. Or patient has not fully recovered from all surgery-related complications to Grade ≤1.
• Has a history of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis.
• Has received bisphosphonate therapy for osteoporosis or symptomatic hypercalcaemia, or denosumab for osteoporosis prior to starting study drug.

Sponsors & Collaborators

• EDDC (Experimental Drug Development Centre), A*STAR Research Entities: lead
• PPD Development, LP: collaborator

Study Sites (11)

University of Arizona Cancer Center, 3838 N. Campbell Avenue, RM 2111, Site 203

Tucson, Arizona, 85719, United States

Location

Chao Family Comprehensive Cancer Center,Stern Center for Cancer Clinical Trials and Research, 101 City Drive South, Site 209

Orange, California, 92668, United States

Location

University of Colorado Hospital Anschutz Cancer Pavilion, 12648 East 17th Avenue; MSF 700, Site 202

Aurora, Colorado, 80045, United States

Location

University of Kansas Medical Center, 4350 Shawnee Mission Parkway, Suite 2310, MS 6004, Site 210

Fairway, Kansas, 66205, United States

Location

Washington University School of Medicine, Siteman Cancer Center, 4921 Parkview Place, Site 205

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center, Duke Cancer Center, 20 Duke Medicine Circle, Site 206

Durham, North Carolina, 27710, United States

Location

Oregon Health and Science University-Knight Cancer Institute, 3485 S Bond Ave., Mail code 0C14CTSite 211

Portland, Oregon, 97239-4501, United States

Location

Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Mail Code Cr 9-4, Site 211

Portland, Oregon, 97239, United States

Location

Department of Investigational Cancer Therapeutics, 1400 Holcombe Blvd., Unit 455, Site 201

Houston, Texas, 77030, United States

Location

National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 7, Site 101

Singapore, 119228, Singapore

Location

National Cancer Centre Singapore, 11 Hospital Drive, Site 102

Singapore, 169610, Singapore

Location

Related Links

• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Endometrial Neoplasms; Ovarian Neoplasms

Interventions

ETC-159; pembrolizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Venkateshan Srirangam Prativadibhayankara

  EDDC, Medical Director

  STUDY DIRECTOR

• Karuppan C Palaniappan

  PPD, Medical Director

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2015
• First Posted: August 13, 2015
• Study Start: October 1, 2015
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: October 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); SG (2)