A study of PRS-344/S095012 (PD-L1x4-1BB bispecific antibody) in patients with solid tumors

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 277

Inclusion Criteria

Age =18 years on the day the consent is signed., Negative test results for human T-lymphotropic virus 1 (HTLV 1). HTLV testing is only required for participants from countries in which HTLV 1 infection is endemic (Japan, countries in the Caribbean basin,South America, Central America, sub-Saharan Africa, and Melanesia)., Dose Escalation: Patients with a histological diagnosis of an unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated., Dose Escalation: Patients must have measurable disease per RECIST 1.1 as assessed by the local site investigator/imaging. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions., Dose Escalation:Patients with no available archived material must have one or more tumor lesions amenable to biopsy, Dose Expansion: Patients with histologically diagnosed Arm 1 and 2: recurrent, persistent, and/or metastatic cervical cancer. Acceptable histologies are squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma. Arm 3: locally advanced or metastatic cutaneous squamous cell carcinoma., Dose Expansion: Patients must have received : Arm 1 (cervical , CPI-naïve): at least 1 prior line of platinum-based combination therapy. Patients must not have received any prior treatment with an immune checkpoint inhibitor (anti-PD-1, PD-L1 or anti-CTLA-4 [cytotoxic T lymphocyte-associated protein 4]) and do not have access to an approved immune checkpoint inhibitor. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients. Arm 2 (cervical cancer, CPI-relapsed/refractory): at least 1 prior line of systemic therapy with an immune checkpoint inhibitor as monotherapy or in combination with chemotherapy and/or any other systemic therapies. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate lternative treatment options for these patients. Arm 3 (CSCC, CPI-relapsed/refractory): at least 1 prior line of systemic therapy with an immune checkpoint inhibitor as monotherapy or in combination with chemotherapy and/or any other systemic therapies. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients., Dose Expansion: Biopsy requirements Arms 1 and 2 (cervical cancer): fresh baseline biopsies are mandatory, on-treatment biopsies are optional. Arm 3 (skin cancer): fresh baseline biopsies are mandatory, on-treatment biopsies are mandatory unless medically contra-indicated., Dose Expansion: Patients must have at least one measurable target lesion as per RECIST 1.1 and/or World Health Organization (WHO) criteria for only externally visible skin tumors confirmed by central review. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions, Patient must have a life expectancy of at least 3 months., Patient should have a documented disease progression on prior therapy before entry into this study, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1., Royal Marsden Prognosis score of 0 to 1 (score based on lactate dehydrogenase (LDH) value, albumin value and number of sites of metastasis)., Adequate organ function as assessed by laboratory tests within 7 days prior to pretreatm

Exclusion Criteria

Patients with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid (= 10 mg/day prednisone or equivalent) is allowed, Patients who have received prior: a. Chemotherapy, small molecule inhibitors, monoclonal antibodies, antibody-drug conjugates, and/or other similar investigational agent: at least 3 weeks or 5 half-lives prior to first IMP administration, whichever is shorter. b. Radioimmunoconjugates or other similar experimental therapies at least 6 weeks or 5 half-lives prior to first IMP administration, whichever is shorter., Patients who have received a 4-1BB agonist in the past., Patients who had a major surgery within 4 weeks prior to first administration of IMP., Patients who have received either systemic corticosteroids (> 10 mg per day or equivalent) or other immunosuppressive medications during the 2 months prior to the first dose of the study drug. Higher single doses of corticosteroids given as premedication against infusion-related reactions are allowed. Treatment with local steroids (inhaled, intranasal, injected are allowed., Patients with an active infection with a viral, bacterial, or fungal pathogen requiring systemic treatment within seven days before first IMP administration., Patients with a history of an opportunistic infection within a year prior to first IMP administration, History of progressive multifocal leukoencephalopathy., Active tuberculosis requiring treatment within 3 years prior to the start of treatment or a suspicion of latent tuberculosis by the investigator.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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