A Phase 1/2 Study of OR502 Alone and in Combination With Other Anti-cancer Agents in Subjects With Advanced Malignancies
This is an open-label, multicenter, first-in-human dose-escalation and expansion Phase 1-2 study designed to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of OR502 administered as a monotherapy and in combination with cemiplimab in subjects with advanced solid tumors.
• Informed consent signed by the subject prior to conducting study-specific procedures.
• Male or female subjects ≥ 18 years of age.
• Histological diagnosis as follows:
∙ Parts A and B (Cohorts A1, A2, and B1): subjects must have a histological diagnosis of any type of carcinoma, sarcoma, or melanoma with progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy with curative intent.
‣ Part B (Expansion Cohorts B2-B3): subjects must have a histological diagnosis of the relevant tumor type (CSCC or PROC) with advanced/metastatic disease not amenable to local therapy with curative intent.
• Prior therapies:
• a. Part A (dose-escalation) and Cohort B1 (monotherapy expansion) i. Subjects must have experienced progressive disease (PD) on an established standard systemic anti-cancer therapy for a given tumor type or have been intolerant to such therapy, or in the opinion of the Investigator have been considered ineligible for a particular form of standard therapy on medical grounds. Subjects must have no available proven curative or life prolonging therapies.
• b. Cohorts B4 and B5 (mini-expansion cohorts) i. Subjects must have received a PD-(L)1 inhibitor-based therapy, either alone or in combination with other anti-cancer agents, for at least 12 weeks. If subjects have received other lines of immunotherapy, including PD-(L)1-based therapy, they must have demonstrated clinical benefit on each prior immunotherapy. Subjects may also have received additional anti-cancer therapies after failure of a PD-(L)1 inhibitor, but 2nd line subjects are preferred.
• c. Cohorts B2 and B3 (dose-expansion) i. Cohort B2 subjects (CSCC) must have received a PD-(L)1 inhibitor. Subjects may not have received an additional immunotherapy.
• ii. Cohort B3 subjects (PROC) must have received platinum-based therapy and experienced disease progression on or within 6 months of completion of such therapy. Subjects may have received prior anti-PD-1 therapy. Subjects may have received additional therapies after failure of platinum-based therapy.
• Subjects must have measurable disease per RECIST v1.1.
• People of childbearing potential, if not postmenopausal (defined as no menses for at least 12 continuous months prior to study entry) or surgically sterile, must be willing to practice at least one of the highly effective methods of birth control described in Section 4.3 for at least a menstrual cycle (or partner's menstrual cycle, for male subjects) before and for 4 months after study medication administration.
• Resolution of prior clinically significant therapy-related AEs (excluding alopecia and ≤ Grade 2 peripheral neuropathy) to ≤ Grade 1 per NCI-CTCAE version 5.0, and no treatment for these AEs for at least 2 weeks prior to the time of enrollment. Electrolyte and hormonal supplementation may be used to treat these AEs provided the subject is stable on these supplements.
• Minimum of 2 weeks since the last dose of other hormone therapy and 3 weeks since the last dose of other systemic cancer therapy or radiotherapy (\> 4 weeks in case of nitrosoureas or radio-immuno conjugate therapy). Adjuvant hormonal therapy (e.g., tamoxifen) is allowed provided the original tumor diagnosis was more than 3 years before the first dose of study medication. Subjects with prostate cancer on stable doses of anti-hormone treatment may remain on therapy for this trial.
• Subjects must have adequate organ function.
⁃ Biopsy specimens:
• All subjects must be able to supply an archival tumor tissue specimen. If an archival specimen is not available, subjects may remain eligible with approval of the medical monitor.
∙ Subjects in Cohort B1 must consent to pre- and on-treatment biopsies. Tissue obtained for the biopsy must not be previously irradiated. No systemic anti-neoplastic therapy may be received by the subject between the time of the biopsy and the first administration of study medication.
∙ Subjects in all other cohorts will be asked to consent to pre- and on-treatment biopsies for biomarker analysis of the acquired tissue. These biopsies are optional and not required for study participation. Tissue obtained for the biopsy must not be previously irradiated. No systemic anti-neoplastic therapy may be received by the subject between the time of the biopsy and the first administration of study medication.
⁃ Subject is able and willing to comply with the protocol and the restrictions and assessments therein.
⁃ As required by local regulations or law, subjects must fulfill the obligation of affiliation or beneficiary of a social security or similar scheme.