Clinical trial NCT04809805: A Study to Learn How Safe BAY2666605 is, How it Affects the Body, How it Moves Into, Through and Out of the Body, the Maximum Amount That Can be Given and Its Action Against Tumors in Adult Participants With Skin Cancer That Has Spread to Other Parts of the Body and Other Types of Advanced Cancer
Official title: An Open Label, Phase 1, First-in-human, Study to Evaluate Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics and Tumor Response Profile of Schlafen12 Complex Inducer (SLFN12 ci) BAY 2666605 in Participants With Metastatic Melanoma and Other Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Melanoma and Other Solid Tumors
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2021-03-22
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: Researchers are looking for a better way to treat people who have advanced cancer.

In this study researchers want to learn more about a new substance called BAY2666605. BAY2666605 triggers the formation of a complex of two proteins called SLFN12 and PDE3A. This complex drive cancer cells into cell death by a mechanism called apoptosis. The complex is only formed in the cancers which contain both proteins.

This study is done in adult patients who have certain types of advanced cancers that cannot be cured by drugs that are currently available. The cancer types include skin cancer that has spread to other parts of the body and cancer that started in the bones or soft tissue, the ovaries, or the brain. Patients with these cancers are only included if the cells of the patient's cancer contain the building plan to produce SLFN12-phosphodiesterase 3A (PDE3A) complex. To confirm this, a specific test is performed with the cancer cells.

The researchers will study how BAY2666605 moves into, through and out of the body. Researchers will try to find the best dose that can be given, how safe BAY2666605 is and how it affects the body. Researchers will also study the action of BAY2666605 against the cancer. Part A will include about 36 participants and up to another 12 participants. Part B will include about 41 participants. All of the participants will take BAY2666605 by mouth as either a liquid or as tablets.

During the study, the participants will take the treatment in 4 week periods called cycles. In each cycle, the participants will in general take BAY2666605 once daily. The participants may also be asked to do overnight fasting before the intake of substance and to have standard high-fat, high-calorie breakfast on some days before taking the dose.

These 4 week cycles will be repeated throughout the trial. The participants can take BAY2666605 until their cancer gets worse, until they have medical problems, or until they leave the trial. Participants will have around 18 visits in each cycle. Some of the visits can also be done via Phone.

During the trial, the study team will take blood and urine samples, do physical examinations and check the participants' heart health using an electrocardiogram (ECG) and an ultrasound of the heart. The study team will also take pictures of the participants' tumors using CT or MRI scans. The study team will ask how the participants are feeling, if participants have any medical problems or if participants are taking any other medicine. About 1 month and 3 months after the last dose, the participants will have another visit and a phone call respectively where participants will be checked for and asked about medical problems. The researchers will then contact the participants every 3 months until the trial ends.


Eligibility criteria: Inclusion Criteria:

Pre-screening:

* Signed informed consent for pre-screening
* Male or female participants aged ≥ 18 years
* Participants with histologically confirmed diagnosis of melanoma, glioblastoma/anaplastic astrocytoma, sarcoma or epithelial ovarian cancer/fallopian tube/primary peritoneal cancer
* Availability of archival tumor tissue (5-10 for prescreening, further 20 to be provided at screening)
* ECOG ≤2

Main Screening :

* Positive SLFN12/PDE3A expression in archival tumour
* Minimum life expectancy at least 12 weeks
* Documented radiological disease progression after treatment with all available standard of care therapies for advanced/metastatic disease and at least one measurable lesion
* Adequate bone marrow, liver, and renal function
* Adequate blood clotting
* Left ventricular ejection fraction \>50%
* All AEs due to previous therapies to CTCAE Grade ≤1. Grade ≤2 neuropathy, fatigue, alopecia, or anorexia, for which further resolution is not expected, may be eligible.
* Negative pregnancy test and use of highly effective contraception
* Signed informed consent for main screening

Exclusion Criteria:

Pre-screening:

* Any malabsorption conditions
* Known HIV infection, active HBV or HCV infection
* Known hypersensitivity to PDE3 inhibitors, or excipients in the formulation; concomitant treatment with any other PDE3 inhibitors
* Participants with clinically relevant cardiovascular diseases and/or relevant ECG findings
* Participants with history of hemorrhage, bleeding disorders or platelet function abnormalities, aneurysm or aneurysmal vasculopathy; Participants with arterial thromboembolic events (ATEs) or venous thromboembolic events (VTEs), including transient ischemic attacks or pulmonary embolism within 6 months before the start of BAY 2666605 or deep vein thrombosis within 3 months before the start of BAY 2666605; Participant with a history of gastrointestinal (GI) ulcerations or perforation, fistula formation involving any internal organs.

Main screening

* Moderate or severe hepatic impairment
* History of organ allograft transplantation, including allogeneic bone marrow
* Previous of co-existing cancer(s) distinct in primary site or histology from the cancer evaluated in this study (with few exceptions)
* Participants with any history of primary meningeal tumors and/or Any active symptomatic or untreated central nervous system (CNS) metastases and/or a number of prior and concomitant therapies
* Major surgery, significant trauma, serious non-healing wound, wound healing complications, ulcer or bone fracture within 4wks prior to 1st dose

Primary outcomes:
measure: Incidence and severity of TEAEs including TESAEs
timeFrame: Up to 6 months after the last participant's first study intervention or until the end of the study, whichever comes first.
measure: The incidence of DLTs at each dose level in the Dose Escalation part of the study
timeFrame: Up to 28 + 14 days
measure: Maximal plasma exposure (Cmax) of BAY2666605
timeFrame: Cycle 1 Day 1
measure: AUC(0-24) of BAY2666605
timeFrame: Cycle 1, Day 1
measure: RP2D of BAY2666605
timeFrame: Up to 6 months after the last participant's first study intervention or until the end of the study, whichever comes first.
measure: Cmax,md of BAY2666605
timeFrame: Cycle 1, Day 15
measure: AUC(0-24)md of BAY2666605
timeFrame: Cycle 1, Day 15
Secondary outcomes:
measure: ORR
timeFrame: Up to 6 months after the last participant's first study intervention or until the end of the study, whichever comes first.
measure: DCR
timeFrame: Up to 6 months after the last participant's first study intervention or until the end of the study, whichever comes first.
measure: DOR
timeFrame: Up to 6 months after the last participant's first study intervention or until the end of the study, whichever comes first.
measure: PFS by investigator assessment
timeFrame: Up to 6 months after the last participant's first study intervention or until the end of the study, whichever comes first.
measure: OS
timeFrame: Up to 6 months after the last participant's first study intervention or until the end of the study, whichever comes first.
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Development Innovations
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics | START San Antonio
state: Texas
Study officials:
References: