A Phase 1 First-In-Human Study of the Anti-CD73 IPH5301 Alone or in Combination With Chemotherapy and Trastuzumab in Patients With Advanced Solid Tumors
CHANCES-IPC 2021-008 is First In Human, Phase I, multicenter, European study evaluating an anti-CD73, IPH5301 in advanced and/or metastatic cancer. The trial will be conducted in two parts, Part I- Dose escalation: This part aims to identify the maximum tolerated dose (MTD) of IPH5301 agent in monotherapy and recommended phase 2 dose (RP2D) for future trials, followed by a safety expansion study part cohort. Part II- Expansion cohort: A total of 12 HER2-expressing breast cancer patients is planned to be enrolled into the next expansion cohort to select a recommended dose of IPH5301 to be administered in combination with chemotherapy and trastuzumab for evaluation in future trials with selected advanced solid tumors.
• Patients with incurable advanced and/or metastatic cancer.
• Patients with any of the following cancers:
‣ In dose escalation: carcinoma of the breast, stomach, esophagus, pancreas, endometrium, ovary or lung.
⁃ In cohort expansion : carcinoma of the breast that expresses HER2. Eligibility is based on HER2 expression as determined locally. HER2-positive is defined by IHC 3+ or gene amplification by in situ hybridization and HER2-low is defined by IHC 1+ or 2+ and no gene amplification by in situ hybridization.
• Prior treatment with at least one prior systemic therapy in the advanced metastatic setting
‣ Dose escalation: no limit on number of prior systemic therapies and considered as failing standard therapeutic alternatives and candidate to a phase I study by a multi-disciplinary tumor board.
⁃ Cohort expansion: patients must have previously re-ceived (or be considered as non-eligible to) all authorized standard treatments as described below :
• HER2-positive breast cancer patient must have received prior (or be considered as ineligible to) trastuzumab +/- pertuzumab-based chemotherapy, trastuzumab deruxtecan, and could have received, trastuzumab emtansine, and capecitabine+anti-HER2 (trastuzumab, lapatinib or trastuzumab tucatinib) according to label.
• HER2-low breast cancer patients must be candidate to paclitaxel-based chemotherapy according to standard guidelines (i.e. must have received and demonstrated resistance to prior endocrine therapy in combination with CDK4/6 inhibitor if estrogen receptor (ER) and/or progesterone receptor (PR),-positive breast cancer; must have received trastuzumab deruxtecan if ER and/or PR-positive breast cancer and candidate to second-line chemotherapy or beyond ; must have received previous immune checkpoint inhibitor-based chemotherapy if first line-treated PD-L1-positive triple-negative breast cancer; must have received sacituzumab govitecan if triple-negative breast cancer previously treated by at least 2 regimen of cytotoxic chemotherapy, including one line in the metastatic setting ; must have received PARP inhibitors if germline BRCA mutation; must have demonstrated no disease progression within 12 months of any taxanes-based previous chemotherapy)
• Presence of at least one measurable lesion by RECIST outside of the CNS.
• At least 18 years of age.
• ECOG performance status of ≤1.
• For patients included in cohort expansion, adequate echocar-diogram, with a left ventricular ejection fraction ≥55%. Patients with a history of LVEF decline (\< 50%) on anti-HER2 treatment will not be allowed to participate.
• For patients included in the cohort expansion, feasibility of obtaining tumor biopsy at study entry.
• All non-hematological AEs related to prior therapy must have completely resolved or improved to Grade 1 prior to screening for this study (except for alopecia).