E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language | |
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | [USA only] Part A: -To evaluate the safety and tolerability of OR2805 when given alone or in combination with cemiplimab or docetaxel to subjects with advanced solid tumors -To determine the recommended dose and regimen of OR2805 when given alone or in combination with cemiplimab or docetaxel for further development Part B: To further evaluate the safety and tolerability of OR2805 when given alone or in combination with cemiplimab or docetaxel to subjects with melanoma or non-small cell lung cancer Part C: To further evaluate the safety and tolerability of OR2805 when given alone or in combination with cemiplimab or docetaxel to subjects with melanoma or nonsmall cell lung cancer | |
E.2.2 | Secondary objectives of the trial | [USA only] Part A: To characterize the serum pharmacokinetics (PK) of OR2805 when given alone or in combination with cemiplimab or docetaxel to subjects with advanced solid tumors Part B: -To assess the anti-tumor activity of OR2805 alone and in combination with cemiplimab or docetaxel in subjects with melanoma or non-small cell lung cancer - To characterize the serum PK of OR2805 when given alone or in combination with cemiplimab or docetaxel to subjects with melanoma or non-small cell lung cancer - To characterize the immunogenicity of OR2805 when given alone or in combination with cemiplimab or docetaxel to subjects with melanoma or non-small cell lung cancer Part C: To assess the anti-tumor activity of OR2805 alone and in combination with cemiplimab or docetaxel in subjects with melanoma or non-small cell lung cancer | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | 1. Male or female subjects ≥ 18 and ≤ 100 years of age. 2. Histological diagnosis as follows: Part B (expansion Cohorts B1-B3): subjects must have a histological diagnosis of the relevant tumor type (NSCLC or melanoma) with advanced/metastatic disease not amenable to local therapy. a. Part C (biology cohort): subjects must have a 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. 3. 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. 4. Prior Therapies: Part B: (dose-expansion) -Part B1 subjects (NSCLC) must have received platinum-based therapy, unless contraindicated, and a PD-1 or PD-L1 inhibitor. - For melanoma: subjects must have received a PD-1 inhibitor, alone or in combination with another immunotherapy. 5. 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. 6. 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. 7. Subjects must have adequate organ function. 8. 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. 9. Subject is able and willing to comply with the protocol and the restrictions and assessments therein. | |
E.4 | Principal exclusion criteria | 1. Subject previously had a severe hypersensitivity reaction to treatment with another mAb. 2. Subject has ECOG PS > 2. 3. Life expectancy < 12 weeks. 4. Prior organ or stem cell transplant. 5. Subjects with symptomatic ascites or pleural effusion. Subjects who are clinically stable for at least 2 weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis) are eligible. 6. Subject has a known active CNS primary tumor or metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no radiological evidence of new or enlarging brain metastases, and are off steroids or on a stable dose up to an equivalent of prednisone 10 mg/day for at least 15 days prior to first dose of study medication. Subjects who have symptoms consistent with CNS metastasis must have a negative MRI during the screening period. 7. Subject has a known history of a hematologic malignancy, malignant primary brain tumor, or another malignant primary solid tumor (other than that under study), unless the subject has undergone potentially curative therapy with no evidence of that disease for at least 3 years. 8. Recent or ongoing serious infections. 9. Autoimmune disease or inflammatory condition requiring systemic therapy. 10. Use of systemic corticosteroids within 15 days or other immunosuppressive drugs within 30 days prior to start of the study, with the exception of corticosteroids as replacement therapy up to an equivalent of prednisone 10 mg/day which are allowed. 11. Subject has received an investigational product or been treated with an investigational device within 30 days prior to first administration of study medication. 12. For Part B: a. Known contraindication to receiving cemiplimab. b. Interstitial lung disease. c. Prior pneumonitis requiring systemic corticosteroid therapy. d. Receiving immunosuppressive therapy. e. A history of severe immune-related adverse reactions from treatment with ipilimumab, defined as any grade 4 toxicity or grade 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for more than 12 weeks. 13. Subject is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study. | |
E.5 End points |
E.5.1 | Primary end point(s) | •Proportion of subjects who experience dose-limiting toxicities (DLTs) as judged by the SRC • Type, frequency, and severity of adverse events (AEs) graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0, including serious adverse events (SAEs) and deaths • Clinical laboratory values, including hematology, coagulation, serum chemistry, and urinalysis | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | DLTs are assessed in Part A (USA participation only); AEs and lab values are monitored throughout the course of the trial. | |
E.5.2 | Secondary end point(s) | • Serum concentrations of OR2805 • Pharmacokinetic parameters: half-life (t1/2), maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under the curve (AUC), minimum concentration (Cmin), clearance (CL), volume of distribution at steady state (Vss), and volume of distribution during the terminal phase (Vz). | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | PK is assessed throughout participation in the trial. Frequent testing of PK is assessed from C1-C4. Intermittent PK is assessed after C4. | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 | The trial involves single site in the Member State concerned | No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | United States | France | Spain | Italy | |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | LSLV: The end of the entire study is defined as the last follow-up for the last subject at any site. | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 30 |