A Study to Investigate APL-5125 in Adults With Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Colorectal Cancer; Gastric Adenocarcinoma; Cholangiocarcinoma; Ovarian Cancer; Prostate Cancer; Appendiceal Adenocarcinoma; Endometrial Adenocarcinoma; Pancreatic Adenocarcinoma; Triple Negative Breast Cancer
• Interventions: Drug: APL-5125

• Registration Number: NCT06399757
• Lead Sponsor: Apollo Therapeutics Ltd

Brief Summary

This is an open-label, Phase 1/2 study to determine the safety, tolerability, and efficacy of APL-5125 for the treatment of selected locally advanced or metastatic solid tumors with particular focus on Colorectal carcinoma (CRC).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-01
• Study First Submitted QC: 2024-05-01
• Study First Posted: 2024-05-06
• Study Start: 2024-06-18
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-14
• Last Update Posted: 2025-02-18
• Primary Completion: 2027-04
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• 18 years or older

• Phase 1: Histologically confirmed locally advanced, inoperable, or metastatic tumor; Colorectal carcinoma, Cholangiocarcinoma, Appendiceal adenocarcinoma.

• For Phase 1 sub-studies: Colorectal carcinoma, Cholangiocarcinoma, Appendiceal adenocarcinoma, Pancreatic Adenocarcinoma, Gastric Adenocarcinoma, Endometrial Adenocarcinoma, Triple Negative Breast Cancer, Ovarian Cancer, Prostate Cancer

• Phase 2: Colorectal carcinoma

• No available standard of care therapy or participant is ineligible for standard of care therapy, except in CRC tumor type in which participant must have previously received all the following therapeutic agents:

  • fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy
  • an anti-VEGF therapy
  • if wt-RAS (wt-KRAS and wt-NRAS), an anti-EGFR therapy

• Eastern Cooperative Oncology Group (ECOG) ≤1

• Body Weight ≥40 kg.

• Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must be willing to use specific contraception or avoid intercourse

• Male participants must be willing to use specific contraception and not plan to impregnate a female partner or donate sperm while on study

• Participant must be willing and able to provide written informed consent and to comply with the requirements of the trial

Exclusion Criteria

• Certain medical conditions such as: active brain metastases, carcinomatous meningitis, unstable angina pectoris, myocardial infarction or clinically significant ventricular arrhythmias, symptomatic congestive heart failure, uncontrolled active infection, history of significant hemorrhage within 4 weeks of the first dose date, intestinal disease or major gastric surgery, arterial thrombosis within 6 months of screening

• Certain prior therapies such as: anti-cancer treatment within 2 weeks of Cycle 1 Day 1, prior radiotherapy within 14 days before screening, active anti-coagulation therapy, over the counter or prescription medications within 14 days or 5 half-lives prior to cycle 1 day 1, herbal medicines and supplements within 14 days

• Major surgery within 1 month of screening

• Hemoglobin < 9.0 g/dL

• Absolute neutrophil count < 1.5 x 10^9/L

• Platelet count < 100 x 10^9/L

• Hepatic function:

  1. Aspartate aminotransferase and/or alanine aminotransferase (ALT) >3 × upper limit of normal (ULN) (>5 x ULN for subjects with liver metastases)
  2. Total bilirubin >1.5 × ULN (except participants with Gilbert's syndrome).
  3. Albumin < 3 g/dL

• Calculated or measured creatinine clearance of <60 mL/minute calculated using the formula of Cockcroft and Gault ([140 - Age] × Mass [kg] / [72 × serum creatinine mg/dL]). Multiply result by 0.85 if female.

• Fridericia's corrected QT interval (QTcF) >470 msec or a family history of Long QT Syndrome.

• Cardiac function: Echocardiogram (or MUGA) showing Left Ventricular Ejection Fraction (LVEF) <45% at rest

• Infectious diseases: positive for HIV (unless controlled with active retroviral therapy), hepatitis B and hepatitis C

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1: Dose Escalation	APL-5125	Dose escalation with increasing dose levels of APL-5125 to identify Recommended Phase 2 Dose. Possibility to expand into select populations
Phase 2: Dose Expansion/Optimization	APL-5125	At least 2 dose levels of APL-5125 in a selected population

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment Emergent Adverse Events [Safety]	Through study completion, approximately one year	Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, electrocardiogram results.
Incidence of dose limiting toxicities [Tolerability] (Phase 1)	Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)	Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs and electrocardiogram results
Determine Recommended Phase 2 Dose (RP2D) levels of APL-5125 in participants with selected advanced solid tumors (Phase 1)	Approximately one year
Assess the anti-tumor activity of APL-5125 in patients with Colorectal carcinoma (Phase 2)	Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)	Response is assessed per RECIST version 1.1 criteria

Secondary Outcome Measures

Name	Time	Method
Assess the preliminary anti-tumor activity of APL-5125 in colorectal carcinoma patients (Phase 1)	Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)	Response is assessed per RECIST version 1.1 criteria
Assess the pharmacokinetics (PK) of APL-5125 (Phase 1)	On days 1, 2 ,4, 8, 15 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).	Evaluate PK parameters: volume of distribution
Further assess the anti-tumor activity of APL-5125 (Phase 2)	Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)	Response is assessed per RECIST version 1.1 criteria
Incidence of treatment emergent adverse events [Further Safety] (Phase 2)	Through study completion (approximately 2 years)	Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, electrocardiogram results
Further assess the PK of APL-5125 (Phase 2)	On days 1 and 8 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).	Evaluate PK parameters: volume of distribution

Trial Locations

Locations (9)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

City of Hope; 🇺🇸 Duarte, California, United States

City of Hope Orange County Lennar Foundation Cancer Center; 🇺🇸 Irvine, California, United States

Florida Cancer Specialists & Research Institute; 🇺🇸 Sarasota, Florida, United States

Duke Cancer Institute; 🇺🇸 Durham, North Carolina, United States

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

Mary Crowley Cancer Research; 🇺🇸 Dallas, Texas, United States

NEXT Oncology- San Antonio; 🇺🇸 San Antonio, Texas, United States