This is a Phase 1b dose escalation trial of OMTX705, an anti-fibroblast activation protein (FAP) antibody-drug conjugate (ADC), in combination with gemcitabine/nab-paclitaxel and tislelizumab in patients with advanced/metastatic pancreatic ductal adenocarcinoma (PDAC).
The trial will be conducted in two parts (Part 1 and Part 2). Both parts will enroll participants with advanced PDAC that, in general, are eligible to receive gemcitabine/nab-paclitaxel. Part 1 is intended to determine the safe recommended dose of OMTX705 in combination with gemcitabine/nab-paclitaxel (1A) and in combination with gemcitabine/nab-paclitaxel+tislelizumab (1B). Both 1A and 1B will enroll in a standard 3+3 design. Only one dose level of OMTX705 will be selected for Part 2 by a Data Safety Monitoring Board (DSMB). In Part 2, 3 parallel randomized arms will be opened simultaneously with 1:1:1 randomization (N=15 each): OMTX705+gemcitabine/nab-paclitaxel (arm 2A), OMTX705+tislelizumab+gemcitabine/nab-paclitaxel (arm 2B) and gemcitabine/nab-paclitaxel (arm 2C, reference arm).
Capable of giving signed informed consent.
Male and female participant aged 18 years and older.
Participants must have histologically or cytologically confirmed PDAC: a) Metastatic PDAC who have not received therapy or received 1 prior line of systemic cytotoxic therapy (Part 1 and Part 2) and if trial treatment is given in the second line setting; b) Non-resectable locoregional PDAC who have not received therapy or received 1 prior line of systemic cytotoxic therapy (Part 1 only); c) A previous treatment with a targeted agent (for example KRAS inhibitor in the context of a clinical trial) without chemotherapy not counted as previous line of therapy. This situation should be discussed with the medical monitor.
Participants should have documented disease progression if previously locally advanced disease or be in 2nd line for stage IV or, in the opinion of the investigator, despite of lack of documented PD per image, require a change in the therapy.
Prior treatment with OMTX705 or nab-paclitaxel for the locally advanced (adjuvant or neoadjuvant) for metastatic disease. Previous use of gemcitabine as radiosensitizer or as part of neoadjuvant/adjuvant therapy is allowed if the treatment was completed 6 months before consent signature. Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies including anti-cytotoxic T-lymphocyte associated protein 4, anti-PD-1, and anti-PD-L1 therapeutic antibodies or any immune checkpoint inhibitor (except for participants to be enrolled in Part 1A).
Treatment with systemic anticancer treatments, investigational products, or major surgery within 4 weeks before the first dose of study drug or 5 half-lives, whichever is shorter. Participants should have recovered from previous treatment toxicity to Grade 1, baseline (excluding anemia, lymphopenia, alopecia, and skin pigmentation). Participants with endocrinopathies should have the replacement treatment in stable dosing.
History of uncontrolled brain metastasis. Participants with brain metastases are allowed if they are previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery and have brain imaging during screening confirming that brain metastasis are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either MRI or CT and considered controlled with ≤10 mg/day prednisone equivalent at the time of receiving the first dose of OMTX705). For asymptomatic participants, screening brain imaging is not required.
Participant has received extended field radiotherapy ≤4 weeks before the start of treatment (≤1 week for limited field radiation for palliation), and who has not recovered to Grade 1 or better from related side effects of such therapy (except for alopecia).