A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents

Inclusion Criteria

• •1. Informed consent signed by the subject prior to conducting study-specific procedures.
• •2. Male or female subjects ≥ 18 and ≤ 100 years of age.
• •3. Histological diagnosis as follows:
• •1. Part A (dose-escalation Cohorts A1-A3): histological diagnosis of any type of carcinoma, sarcoma, or melanoma with progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy.
• •2. Part B (expansion Cohorts B1-B3): histological diagnosis of the relevant tumor type (NSCLC or melanoma) with advanced/metastatic disease not amenable to local therapy.
• •a. Part C (biology cohort): histological or cytological diagnosis of any type of carcinoma, sarcoma, or melanoma with progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. At least 10 subjects each must have a diagnosis of SCCHN, dedifferentiated liposarcoma, or leiomyosarcoma with prior treatment described below.
• •4. Prior therapies:
• •a. Part A (dose-escalation) i. Subjects must have experienced 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. Part B (dose-expansion) i. Part B1 subjects (NSCLC) must have received platinum-based therapy, unless contraindicated, and a PD-1 or PD-L1 inhibitor. Subjects eligible for targeted therapies to EGFR, ALK, ROS, RET or NTRK (e.g., crizotinib) must have previously received and exhausted such therapies. Prior therapies may have been administered alone or in combination. Subjects must have received prior PD-(L)1-based therapy as the most recent prior therapy and demonstrated progression while on that therapy.
• •ii. Part B2 subjects (NSCLC) must have received platinum-based therapy and a PD-1 or PD-L1 inhibitor unless contraindicated. Subjects eligible targeted therapies to EGFR, ALK, ROS, RET or NTRK (e.g., crizotinib) must have exhausted such therapies. Prior therapies may have been administered alone or in combination. Part B2 subjects may have received a total of 3 lines of prior therapy and are not required to have received a PD-(L)1-based therapy as the most recent therapy.
• •iii. For melanoma: subjects must have received a PD-1 inhibitor, alone or in combination with another immunotherapy. Eligible subjects may have received BRAF- and MEK-targeted therapies. Subjects must have received prior PD-1-based therapy as the most recent therapy and demonstrated radiographic progression while on that therapy.
• •c. Part C (biology cohort): subjects other than those with liposarcoma, leiomyosarcoma, or SCCHN must have experienced PD on an established standard medical 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 and must have no available demonstrated curative or life-prolonging therapies. Subjects with liposarcoma must have dedifferentiated liposarcoma, have received at least 1 prior systemic therapy, and require additional treatment. For leiomyosarcoma, subjects must have received at least 1 prior therapy for advanced or metastatic disease. For SCCHN, subjects must have received 1 prior line of chemotherapy and a PD-1- or PD-L1-targeted agent alone or in combination with chemotherapy unless contraindicated. No more than 2 chemotherapy regimens in the advanced setting for SCCHN are allowed. All subjects must have demonstrated progression on the most recent line of therapy.
• •5. Subjects must have measurable disease per RECIST v1.1. Subjects in Part C must have at least one 1 lesion amenable to biopsy and that is not to be used for response assessment per RECIST v1.1.
• •6. If not postmenopausal or surgically sterile, subjects must be willing to practice at least one of the following highly effective methods of birth control for at least a menstrual cycle (or partner's menstrual cycle, for male subjects) before and for 3 months after study medication administration: (1) true abstinence, when this is in line with the preferred and usual lifestyle of the subject, from sexual intercourse with a member of the opposite sex; (2) sexual intercourse with vasectomized male/sterilized female partner; (3) hormonal female contraceptive (oral, parenteral, intravaginal, implantable, or transdermal) for at least 3 consecutive months prior to investigational product administration (when not clinically contraindicated as in breast, ovarian, and endometrial cancers); (4) use of an intrauterine contraceptive device or intrauterine hormone-releasing system.
• •7. Resolution of prior-therapy-related AEs (excluding alopecia and grade ≤ 2 peripheral neuropathy) to ≤ grade 1 per CTCAE v5.0, 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.
• •8. 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 (for example tamoxifen) is allowed provided the original tumor diagnosis was more than 3 years before the first dose of study medication.
• •9. Subjects must have adequate organ function.
• •10. All subjects must be able to supply an archival tumor biopsy specimen. For Part C (biology cohort), subjects must consent to a newly obtained tumor biopsy (that can be biopsied based on Investigator's assessment) and to providing the acquired tissue for biomarker analysis. An additional on-treatment biopsy is required for subjects in Part C.
• •11. Subject is able and willing to comply with the protocol and the restrictions and assessments therein.