Clinical trial NCT05858164: A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors
Official title: An Open-label, Phase 1, First-in-human, Dose Escalation Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics, and Tumor Response Profile of the Diacylglycerol Kinase Alpha Inhibitor (DGKαi) BAY 2862789 in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Non-small Cell Lung Cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2023-05-15
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Researchers are looking for a better way to treat people who have advanced solid tumors including a specific kind of lung cancer (non-small cell lung cancer, NSCLC).

Advanced solid tumors are types of cancer that have spread to nearby tissue, lymph nodes, and/or to distant parts of the body and that are unlikely to be cured or controlled with currently available treatments.

BAY2862789 works by blocking an enzyme in T-cells, thereby activating them. T-cells are a type of immune cell that are known to have an anti-cancer effect.

The main purpose of this first-in-human study is to learn:

* how safe different doses of BAY2862789 are,
* the degree to which medical problems caused by BAY2862789 can be tolerated (also called tolerability),
* what maximum amount (dose) can be given, and
* how BAY2862789 moves into, through and out of the body.

To answer this, the researchers will look at:

* the number and severity of medical problems participants have after taking BAY2862789 for each dose level. These medical problems are also referred to as adverse events. An adverse event is considered "serious" when it leads to death, puts the participants' lives at risk, requires hospitalization, causes disability, causes a baby being born with medical problems or is otherwise medically important.
* the (average) total level of BAY2862789 in the blood (also called AUC) after intake of single and multiple doses.
* the (average) highest level of BAY2862789 in the blood (also called Cmax) after intake of single and multiple doses.

Doctors and their team keep track of all medical problems that participants have during the study, even if they do not think the medical problem might be related to the study treatment.

In addition, the researchers want to know if and how the participants' tumors change after taking BAY2862789.

The dose escalation will be done to find the most appropriate dose that can be given. For this, each participant will receive one of the increasing doses of Bay 2862789. More groups might be investigated based on new data that emerges. For this, each participant will receive one of the increasing doses of BAY2862789.

Participants in the study will take the study treatment until their tumor gets worse (also known as 'disease progression'), until they have medical problems, until they leave the study, or until the study is terminated.

Each participant will be in the study for several months, including a test (screening) phase of up to 28 days, few months of treatment depending on the participant's benefit, and a follow up phase after the end of treatment. The following approximate numbers of visits to the study site are planned: two during the screening phase, six in the first treatment month, one to three per month in the following periods.

During the study, the study team will:

* take blood and urine samples
* do physical examinations
* check vital signs such as blood pressure, heart rate, body temperature
* examine heart health using ECG (electrocardiogram)
* check cancer status using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scans
* take tumor samples (if required)
* pregnancy test

The treatment period ends with a visit no later than 7 days after the last BAY2862789 dose. The study doctors and their team will check the participants' health and any changes in cancer about 30 and 90 days after the last dose and every 12 weeks thereafter. This follow-up period ends if the cancer worsens, if a new anti-cancer treatment is started, or until the participant leaves the study. In addition, the study doctors and their team will contact the participant every 12 weeks to learn about the participant's survival. This ends no later than 12 months after the last participant started treatment or by the end of the study, whichever comes first.

If the study participant benefits from treatment, continuation of treatment with BAY2862789 beyond the duration of this study might be possible.


Eligibility criteria: Inclusion Criteria:

* Capable of giving signed informed consent
* Be ≥18 years of age on day of signing informed consent.
* Have measurable disease per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) as assessed by the local site investigator.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Participants with a histologically confirmed diagnosis of a solid tumor that have exhausted available treatments known to be beneficial for this tumor type or for whom these treatments are not acceptable and for whom this trial is a reasonable option for them, will be enrolled onto this study. Appropriate molecular profiling of tumors should have been performed according to local national guidelines prior to trial entry. Specifications for the different parts of the study are below:

  -- Dose escalation: All solid cancers, except primary central nervous system cancers.
* Provision of archival tumor sample at baseline is mandatory for all participants in escalation, and expansion cohorts.
* Participants must be willing to undergo mandatory paired biopsies of tumor (pre- and on- treatment).
* Have adequate organ function.
* Agree to use contraception during the treatment period and for at least 6 months after the last dose of study treatment.

Exclusion Criteria:

* Had an allogeneic tissue/solid organ transplant.
* Previous therapy with a diacylglycerol kinase (DGK) inhibitor
* Has received a prior therapeutic regimen containing an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-programmed cell death 1 ligand 2 (anti PD-L2) agent or an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX 40, CD137) and was discontinued from that treatment regimen due to a Grade 3 or higher immune related adverse event (irAE) or any toxicity that was life-threatening.
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 half-lives, whatever is shorter, prior to treatment. Growth factor treatments such as granulocyte colony-stimulating factor (G-CSF) must have been discontinued 4 weeks prior to entering the study.
* Participants must have recovered from previous radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
* Participants cannot have had a blood transfusion within 2 weeks of starting therapy.
* Has received a live vaccine within 30 days prior to the first dose of study drug.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Participants with new brain metastases on screening brain magnetic resonance imaging/computed tomography (MRI/CT).
* Primary central nervous system malignancy or presence of leptomeningeal disease.
* Participants with gastrointestinal conditions that may compromise oral absorption such as short bowel syndrome or active tumor-related bowel obstruction with ongoing symptoms compromising absorption over last 6 months.
* Has an active autoimmune disease including inflammatory bowel disease that has required systemic treatment in past 2 years.
* Current pneumonitis / interstitial lung disease.
* Has an active infection requiring systemic therapy.

Primary outcomes:
measure: The number and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 90 days after the last administration of the study treatment
measure: Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level in the Dose Escalation part of the study
timeFrame: Up to 21 days after the first administration of the study treatment
measure: Recommended Dose for Expansion (RDE)
timeFrame: Up to 2 years
measure: Maximum concentration (Cmax) BAY2862789 after single-dose
timeFrame: from pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days)
measure: Maximum concentration (Cmax) BAY2862789 after multiple-dose
timeFrame: Pre-dose and up to 24 hours after Day 16 in Cycle 1
measure: Area under the curve (AUC) BAY2862789 after single-dose
timeFrame: from pre-dose up to 24 hours after administration on Cycle 1 Day 1 (each cycle is 21 days)
measure: Area under the curve (AUC) BAY2862789 after multiple-dose
timeFrame: Pre-dose and up to 24 hours after Day 16 in Cycle 1
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Duration of response (DOR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS) at 6 months
timeFrame: Up to 6 months
measure: Overall survival (OS) at 12 months
timeFrame: Up to 12 months
measure: Activation of effector T memory cells
timeFrame: Up to 2 years
measure: Ex vivo stimulated short-term activation of Interleukin 2 (IL2) and interferon-gamma
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Celebration
country: United States
facility: AdventHealth medical Group Oncology Research at Celebration
state: Florida
city: Detroit
country: United States
facility: Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center | Shafi Group
state: Mississippi
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: START | San Antonio
state: Texas
city: Darlinghurst
country: Australia
facility: The Kinghorn Cancer Centre - Medical Oncology Department
state: New South Wales
city: QLD
country: Australia
facility: Princess Alexandra Hospital Australia
state: Queensland
city: Wuhan
country: China
facility: Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.
state: Hubei
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital Ein Kerem
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbugdo
city: Jinju-si
country: Korea, Republic of
facility: Gyeongsang National University Hospital
state: Gyeongsangnam-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Institut d'Oncologia - Grupo de Tumores Toracicos y Cancer de Cabeza y Cuello
city: Malaga
country: Spain
facility: Instituto de Investigacion Biomedica de Malaga (IBIMA) - sede Hospital Universitario Virgen de la Victoria (HUVV)
Study officials:
References: