E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Head and Neck Squamous Cell Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
* Phase 1 part
To evaluate the safety and tolerability of S-488210 in HLA A*02:01-positive patients with head and neck squamous cell carcinoma (HNSCC) receiving 4 vaccinations of S-488210
* Phase 2 part
To compare the overall survival between HLA-A*02:01-positive and HLA-A*02:01-negative patients receiving S-488210 |
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E.2.2 | Secondary objectives of the trial |
* Phase 1 part
To evaluate the specific CTL response
* Phase 2 part
To evaluate:
- The specific CTL response
- The antitumor efficacy
- The safety and tolerability
- Any improvement in general health status based on EORTC QLQ-C30 and QLQ-H&N35 questionnaires
- The progression-free survival
- The overall survival |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Confirmed to be HLA-A*02:01-positive (Phase 1 part only)
2. Has unresectable locoregionally recurrent and/or metastatic HNSCC after failure of platinum based chemotherapy (including patients who are intolerant to platinum based chemotherapy due to adverse or toxic effects)
3. Has previously received platinum based chemotherapy containing either cisplatin or carboplatin as monotherapy or in combination with radiation
4. Has histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
5. Has the presence of measurable disease as defined by response evaluation criteria in solid tumors (RECIST) that is confirmed on imaging within 4 weeks before enrollment
6. Has an ECOG PS of 0 or 1 within 2 weeks before enrollment
7. Has an expected life span of at least 3 months from the time of enrollment
8. Is willing and able to provide a tumor tissue sample
9. Is a male or female aged ≥18 years at enrollment
10. Has been informed of the full nature and purpose of the study, including possible risks and side effects, and has been given ample time and opportunity to read and understand this information, and has signed the ICF
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E.4 | Principal exclusion criteria |
1. Has been treated with 3 or more chemotherapy regimens
2. Is human immunodeficiency virus positive, hepatitis B surface antigen positive, hepatitis C virus positive, or has other positive laboratory tests suggestive of active infection
3. Has human papilloma virus-positive tumor (Phase 2 part only)
4. Has any other malignant disease within the past 3 years, except for cervical carcinoma in situ or skin cancers other than melanoma
5. Has brain metastasis
6. Has received any of the following within 28 days of enrollment: anti malignant tumor drugs, immunosuppressants, corticosteroids, radiation therapy, immunotherapy, thermotherapy, and/or major surgery
7. Has an uncontrolled systemic or active infection
8. Has uncontrolled comorbidities such as hepatic insufficiency, renal insufficiency, heart failure, chronic obstructive pulmonary disease, bleeding disorders, or metabolic disease
9. Has an autoimmune disease including rheumatoid arthritis, systemic lupus erythematosus, or psoriasis
10. Has a current drug allergy or a past history of drug allergy
11. Has a past history of hypersensitivity to vaccines (eg, prophylactic vaccination)
12. Has received any systematic radiation therapy within 28 days of enrollment
13. Has inadequate bone marrow function, hepatic, or renal function test values that meet the following criteria within 2 weeks before enrollment:
- White blood cell count <2000/mm^3 or >20 000/mm^3
- Platelet count <50 000/mm^3
- Aspartate aminotransferase or alanine aminotransferase >5 × the upper limit of the reference range
- Total bilirubin >3 × the upper limit of the reference range
- Serum creatinine >3 × the upper limit of the reference range
14. Is a female who is breastfeeding or pregnant, or who might be pregnant
15. Cannot or does not intend to use adequate means of contraception (barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel]; hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings]; or intrauterine devices) from enrollment until 12 weeks after final study drug administration
16. Has received another investigational product (including clinical study drugs) within 60 days of enrollment
17. Has received another investigational product (including clinical study drugs) within 28 days of enrollment, or still has adverse effects attributable to a previous investigational product at the time of
screening
18. Has previously been genotyped for HLA status (Phase 2 part only) |
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E.5 End points |
E.5.1 | Primary end point(s) |
* Phase 1 part
AE grades assessed by CTCAE Version 4.0; incidence and causality of AEs
* Phase 2 part
Comparison of overall survival between HLA-A*02:01-positive and HLA-A*02:01-negative patients |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Overall survival (OS) will be assessed for the Phase 1 part 6 months after the last patient has completed Step 1 of the Phase 1 part, when all patients complete Step 1 of the Phase 2 part, then 6, 12, and 18 months following completion of Step 1 of the Phase 2 part.
Overall survival will be assessed for the Phase 2 part when all patients complete Step 1 of the Phase 2 part, then 6, 12, and 18 months following completion of Step 1 of the Phase 2 part.
Patients who discontinue the study (either before or after Step 1) will also be followed up at these time points. |
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E.5.2 | Secondary end point(s) |
* Phase 1 part
Immune response, as evidenced by CTL induction rate
* Phase 2 part
- Immune response, as evidenced by CTL induction rate
- Progression free survival
- Overall survival
- Antitumor efficacy, as evidenced by: objective response rate (complete response [CR] + partial response [PR] to the analysis population), overall response rate (CR + PR + stable disease [SD] to the analysis population) according to RECIST Version 1.1
- AE grades assessed by CTCAE Version 4.0; incidence and causality of AEs
- Improvement in the general health status of patients compared with baseline based on the EORTC QLQ-C30 and QLQ-H&N35 questionnaires |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS and PFS Phase 1 6 months after the last patient has completed Step 1 of the Phase 1 part, when all patients complete Step 1 of the Phase 2, then 6, 12 and 18 months following completion of Step 1 of Phase 2.
OS and PFS Phase 2 when all patients complete Step 1 of the Phase 2 part, then 6, 12 and 18 months following completion of Step 1 of the Phase 2 part
Patients who discontinue the study (either before or after Step 1) will also be followed up at these time points.
Blood samples for specific CTL measurement for Phases 1 and 2 at visit 1, 5, 9 and 13.
Tumor evaluation will be assessed every 8 weeks for Phases 1 and 2.
Any improvement in general health status of patients compared with baseline will be assessed every 8 weeks from previous until Visit 25 for Phases 1 and 2. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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
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Date when evaluation of overall survival is completed.
See section 5.6 Study Termination, of the protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 15 |