An Open-label, Phase 1 Dose Escalation and Phase 2 Dose Expansion Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of SMP-3124LP in Adults With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- SMP3124LP
- Conditions
- Solid Tumor
- Sponsor
- Sumitomo Pharma America, Inc.
- Enrollment
- 120
- Locations
- 6
- Primary Endpoint
- Determine the Objective Response Rate (ORR)
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
An Open-label, Phase I Dose Escalation and Phase 2 Dose Expansion Study to Assess Safety, Tolerability, Preliminary Antitumor Activity of SMP 3124LP in Adults with Advanced Solid Tumors
Detailed Description
Phase 1/2, global, multicenter, open-label, first-in-human, clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of SMP-3124
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically-confirmed cancer that is advanced, recurrent, or metastatic with the following origins, and whose disease progressed on standard therapy and for whom there are no alternative therapies that may confer overall survival benefit.
- •For patients in the Dose Escalation part:
- •Platinum-resistant ovarian cancer
- •Histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer, with predominantly high-grade (Grade 2 or 3) epithelial features (serous and clear cell)
- •Platinum resistant is defined as relapsed within 6 months after the last dose of platinum-based therapy
- •Triple negative breast cancer - ER- and PR-negative with HER2 negative
- •HER2 negative is defined as one of the following: 0 or 1+ by IHC, or if IHC 2+, then in situ hybridization is negative per the ASCO-CAP HER2 guidelines
- •ER- and PR-negative is defined as \< 10% of cells expressing hormonal receptors by IHC, as per standard guidelines
- •Squamous cell carcinoma of the anus
- •Patient with locally advanced ineligible for surgery is allowed.
Exclusion Criteria
- •Patient has received prior treatment at any time with a cell cycle checkpoint inhibitor (eg, CHK1 and/or CHK2, WEE1, or ATR inhibition)
- •Patient has a known allergy or sensitivity to any component of SMP-3124LP, including the inactive ingredients
- •Patient has received treatment with systemic anticancer therapy, radiotherapy, or investigational therapy within 14 days prior to Study Cycle 1 Day
- •(Palliative radiotherapy with a limited field of radiation within 2 weeks will be permitted.)
- •Patient has undergone a major surgical procedure ≤ 28 days, or minor surgical procedure ≤ 7 days, prior to Cycle 1 Day 1
- •Patient has used strong CYP1A2 or 2D6 inhibitors within 14 days or 5 half-lives, whichever occurs first, prior to Cycle 1 Day 1 (examples of restricted CYP1A2 and CYP2D6, P-gp, and/or BCRP inducers, inhibitors, or substrates are presented in Table 16)
- •Patient has central nervous system metastasis or leptomeningeal disease
- •Prior or concurrent malignancy whose natural history or treatment would have a significant potential to interfere with the safety or efficacy assessments of the investigational regimen
- •Patient has an abnormal ECG that is clinically significant, including a corrected QT interval (corrected using Fridericia's correction formula \[QTcF\]) \> 470 msec; and/or a history of Torsade de Pointes
- •Patient has a left ventricular ejection fraction \< 45% by echocardiogram (ECHO)
Arms & Interventions
Part 1 - Dose Escalation & Dose Optimization
Patient to receive SMP-3124LP continuous IV infusion every 2 weeks (q2w) (Schedule 1). At the discretion of the Safety Review Committee (SRC), Schedule 2 - IV infusion every 3 weeks (q3w) - may be initiated for example, after a maximum tolerated dose (MTD) is reached for Schedule 1 (q2w) or when 2 or more patients experience a dose delay of at least 7 days at the same dose level for Schedule 1. The provisional dose levels are 20, 40, 60, 90, and 120 mg/m2, and intermediate and additional dose levels may be added as needed.
Intervention: SMP3124LP
Part 2 - Dose Expansion
Patient to receive SMP-3124LP continuous IV infusion at the Recommended Phase 2 Dose as determinated in part 1.
Intervention: SMP3124LP
Outcomes
Primary Outcomes
Determine the Objective Response Rate (ORR)
Time Frame: 6 months
Determination of the Recommended Phase 2 Dose by Assessing Dose-limiting Toxicities (DLTs)
Time Frame: 28 days
Number of Participants With Adverse Events and Serious Adverse Events
Time Frame: 6 months
Secondary Outcomes
- The maximum concentration (Cmax) of SMP-3124 and SMP-3124LP(6 months)
- The area under the curve (AUC) of SMP-3124 and SMP-3124LP(6 months)
- The duration of response (DOR) assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(6 months)