Bayer 21948 - An open-label, phase 1, first-in-human, dose escalation and expansion study to evaluate the safety, tolerability, maximum tolerated or administered dose, pharmacokinetics, pharmacodynamics, and tumor response profile of the diacylglycerol kinase zeta inhibitor (DGKzi) BAY 2965501 as monotherapy, and in combination, in participants with advanced solid tumors

Standard of care regimens for cancers include chemotherapy, immunotherapy, and molecularly targeted therapies. Whilst these have improved survival, outcomes remain poor in many tumours creating a need for new therapies. This trial is the first time BAY2965501 is given to humans. BAY 2965501 inhibits an enzyme in T-cells to activate them. T-cells are immune cells that have an anti-cancer effect. BAY 2965501 will be tested in two parts; firstly, dose escalation will test increasing doses of BAY 2965501 in any cancer that has stopped responding to known therapies, looking at the pharmacokinetics (how the human body absorbs and metabolises Bay2965501), the pharmacodynamics (how BAY2965501 works in the cancer) and the safety of BAY 2965501 in humans. Patients’ symptoms, bloods and tumour samples will be used for this. Alongside dose escalation, to gain more information on how BAY 2965501 works within tumours, patients with tumours of lung cancer, gastric cancer, melanoma or renal cancers will be recruited to test up to 4 specific dose levels of BAY 2965501 with tumour biopsies done before and on treatment. The second part will test the dose(s) of BAY2965501 decided in part one, in lung or gastric cancer patients to assess how well it works in these tumours. A group of these lung cancer patients who receive BAY 2965501 will have a research scan to image their tumours and assess how the immune system interacts with their tumour before and during BAY 2965501 treatment. BAY2965501 will be developed as monotherapy and in combination. The first combination to be tested will be BAY2965501 with pembrolizumab, firstly in dose escalation (in solid tumours) to determine the dose(s) to be tested further in expansion. The expansion cohorts will test BAY2965501 with pembrolizumab in treatment resistant NSCLC, gastric cancer and first line treatment naïve incurable NSCLC.