E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study population will include participants diagnosed with metastatic melanoma, advanced/metastatic urothelial carcinoma (mUC), advanced hepatocellular carcinoma (HCC) in Part 1, and metastatic squamous or non-squamous non-small cell lung cancer (NSCLC), and metastatic renal cell carcinoma (RCC) in Part 2. |
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E.1.1.1 | Medical condition in easily understood language |
melanoma (skin cancer) , bladder cancer, liver cancer in Part 1, and lung cancer, and renal cancer in Part 2.
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064467 |
E.1.2 | Term | Urothelial carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050513 |
E.1.2 | Term | Metastatic renal cell carcinoma |
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 |
- Part 1 Arm A: To describe the pharmacokinetics of ipilimumab with rHuPH20 administered subcutaneously as monotherapy
-Part 2 Arm A: To describe the pharmacokinetics of ipilimumab with rHuPH20 administered subcutaneously in combination with SC nivolumab
-Part 2 Arm B: To describe the pharmacokinetics of ipilimumab administered subcutaneously with rHuPH20 in combination with SC nivolumab with rHuPH20
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E.2.2 | Secondary objectives of the trial |
- Part 1 Arm B: To describe the pharmacokinetics of ipilimumab without rHuPH20 administered subcutaneously as monotherapy
- Part 1 Arm A: To assess the safety profile of SC ipilimumab with rHuPH20 monotherapy followed by ipilimumab and nivolumab IV combination
- Part 1 Arm B: To assess the safety profile of SC ipilimumab without rHuPH20 monotherapy followed by ipilimumab and nivolumab IV combination
- Part 2 Arms A/B: To assess the safety profile of SCipilimumab with rHuPH20 in combination with SC nivolumab with rHuPH20
- Part 1 Arms A/B and Part 2 Arms A/B: To evaluate incidence of AEs in the broad standardized MedDRA query (SMQ) of Anaphylactic Reaction and the select AE hypersensitivity/injection/infusion reaction category
- Part 1 Arms A/B: To assess the immunogenicity of SC ipilimumab
- Part 2 Arms A/B: To assess the immunogenicity of SC ipilimumab and SC nivolumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Men and women must follow methods of contraception as described in the protocol
Part 1 Arms A and B: Metastatic Melanoma
- Previously untreated, histologically confirmed stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system v.8.0
Part 1 Arm A:Advanced/mUC
- Participants with histologically or cytologically confirmed urothelial carcinoma
Part 1 Arm A: Advanced HCC
-Participants with histological confirmation of Hepatocellular Cancer (HCC)
Part 2 Arm A: Metastatic NSCLC
-Participants with histologically confirmed stage IV or recurrent Non Small Cell Lung Cancer (NSCLC)
Part 2 Arm B: Advanced or Metastatic RCC
- Histological confirmation of Renal Cell Carcinoma (RCC)
-ECOG Performance Status of 0 or 1 and for RCC (Part 2 Arm B), Karnofsky performance status >= 70% |
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E.4 | Principal exclusion criteria |
- History of allergy or hypersensitivity to study drug components
Part 1 Arm A: Advanced HCC
- History of hepatic encephalopathy or evidence of portal hypertension
- Active co-infection with hepatitis D virus infection in participants with HBV
Part 2 Arm A:Metastatic NSCLC
-Participants with known ALK translocations and EGFR mutation that are sensitive to available targeted inhibitor therapy
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Part 1 Arm A: Average concentration of ipilimumab (Cavg21d)
2) Part 1 Arm A: Area under the concentration in ipilimumab AUC(0-21d)
3) Part 1 Arm A: Maximum observed serum concentration of ipilimumab (Cmax)
4) Part 1 Arm A: Observed concentration of ipilimumab (C21d)
5) Part 1 Arm A: Time of maximum observed concentration in ipilimumab (Tmax)
6) Part 2 Arm A: Average concentration in ipilimumab (Cavg42d)
7) Part 2 Arm A: Area under the concentration in ipilimumab AUC(0-42d)
8) Part 2 Arm A: Maximum observed serum Concentration of Ipilimumab (Cmax)
9) Part 2 Arm A: Observed concentration in ipilimumab (C42d)
10) Part 2 Arm A: Time of maximum observed concentration in ipilimumab (Tmax)
11) Part 2 Arm B: Average concentration of Ipilimumab (Cavg21d)
12) Part 2 Arm B: Area Under the Concentration in Ipilimumab AUC(0-21d)
13) Part 2 Arm B: Maximum observed serum Concentration in Ipilimumab (Cmax)
14) Part 2 Arm B: Observed concentration of ipilimumab (C21d)
15) Part 2 Arm B: Time of maximum observed concentration in Ipilimumab (Tmax) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Day 21
2) Day 21
3) Up to 21 days
4) Day 21
5) Up to 21 days
6) Day 42
7) Day 42
8) Up to 42 days
9) Day 42
10) Up to 42 days
11) Day 21
12) Day 21
13) Up to 21 days
14) Day 21
15) Up to 21 days |
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E.5.2 | Secondary end point(s) |
1) Part 1 Arm B: Average concentration of ipilimumab without rHuPH20 (Cavg21d)
2) Part 1 Arm B: Area under the concentration in ipilimumab without rHuPH20 AUC(0-21d)
3) Part 1 Arm B: Maximum observed serum concentration of ipilimumab without rHuPH20 (Cmax)
4) Part 1 Arm B: Observed concentration of ipilimumab without rHuPH20 (C21d)
5) Part 1 Arm B: Time of maximum observed concentration in ipilimumab without rHuPH20 (Tmax)
6) Incidence of adverse events (AE's)
7) Incidence of serious adverse events (SAEs)
8) Incidence of AE's leading to discontinuation
9) Incidence of death
10) Incidence of laboratory abnormalities
11) Instance of Anaphylactic occurring within 2 days of study drug administration
12) Instance of hypersensitivity occurring within 2 days of study drug administration
13) Incidence of hypersensitivity occurring within 2 days of study drug administration
14) Incidence of infusion reactions occurring within 2 days of study drug administration
15) Incidence of injection occurring within 2 days of study drug administration
16) Percentage of participants who develop anti-ipilimumab antibodies
17) Percentage of participants who develop anti-nivolumab antibodies
18) Percentage of participants who have developed neutralizing antibodies |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Day 21
2) Day 21
3) Up to 21 days
4) Day 21
5) Up to 21 days
6) Up to 2.5 years
7) Up to 5 years
8) Up to 2.5 years
9) Up to 2.5 years
10) Up to 2.5 years
11) Up to 2.5 years
12) Up to 2.5 years
13) Up to 2.5 years
14) Up to 2.5 years
15) Up to 2.5 years
16) Up to 2.5 years
17) Up to 2.5 years
18) Up to 2.5 years |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient Experience and Preference Questionnaire |
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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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
pharmacokinetics, safety, and tolerability of Ipi SC with or without rhuPh20 alone or with nivo SC |
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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 | No |
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 | No |
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 | 4 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Australia |
Brazil |
France |
Italy |
Netherlands |
New Zealand |
Spain |
United Kingdom |
United States |
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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
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End of trial is defined as last visit or scheduled procedure shown in the Schedule of Activities for the last participant ongoing on study (=last survival follow-up visit of the last participant) |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |