Clinical trial NCT06399757: A Study to Investigate APL-5125 in Adults With Advanced Solid Tumors
Official title: A Phase 1/2 Study to Assess the Safety and Antitumor Activity of APL-5125 in Adults With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Cholangiocarcinoma
Appendiceal Adenocarcinoma
Pancreatic Adenocarcinoma
Gastric Adenocarcinoma
Endometrial Adenocarcinoma
Triple Negative Breast Cancer
Ovarian Cancer
Prostate Cancer
Lead sponsor: Apollo Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2024-05-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events [Safety]
timeFrame: Through study completion, approximately one year
measure: Incidence of dose limiting toxicities [Tolerability] (Phase 1)
timeFrame: Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
measure: Determine Recommended Phase 2 Dose (RP2D) levels of APL-5125 in participants with selected advanced solid tumors (Phase 1)
timeFrame: Approximately one year
measure: Assess the anti-tumor activity of APL-5125 in patients with Colorectal carcinoma (Phase 2)
timeFrame: Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)
Secondary outcomes:
measure: Assess the preliminary anti-tumor activity of APL-5125 in colorectal carcinoma patients (Phase 1)
timeFrame: Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)
measure: Assess the pharmacokinetics (PK) of APL-5125 (Phase 1)
timeFrame: 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).
measure: Assess the pharmacokinetics (PK) of APL-5125 (Phase 1)
timeFrame: 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).
measure: Further assess the anti-tumor activity of APL-5125 (Phase 2)
timeFrame: Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)
measure: Incidence of treatment emergent adverse events [Further Safety] (Phase 2)
timeFrame: Through study completion (approximately 2 years)
measure: Further assess the PK of APL-5125 (Phase 2)
timeFrame: On days 1 and 8 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).
measure: Further assess the PK of APL-5125 (Phase 2)
timeFrame: On days 1 and 8 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Irvine
country: United States
facility: City of Hope Orange County Lennar Foundation Cancer Center
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology- San Antonio
state: Texas
Study officials:
affiliation: Apollo Therapeutics Ltd
name: Sanjay Aggarwal, MD
role: STUDY_CHAIR
References: