E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Melanoma; Non-small cell lung cancer |
|
E.1.1.1 | Medical condition in easily understood language |
skin cancer; lung cancer; eye cancer |
|
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053571 |
E.1.2 | Term | Melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 | 10081431 |
E.1.2 | Term | Uveal melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 | 10079440 |
E.1.2 | Term | Non-squamous non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
To evaluate the antitumor activity of SEA-CD40 combined with other therapies. |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of SEA-CD40 combined with other therapies. - To evaluate control of disease. - To evaluate durability of response in subjects who respond to study drug(s). - To evaluate PFS and survival. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed unresectable malignancy defined as one of the following: a. Cohort 1: Relapsed and/or refractory metastatic melanoma • Uveal/ocular melanoma is excluded • Subjects may have received up to 3 prior lines of systemic therapy for advanced disease (prior adjuvant/neoadjuvant immunotherapy such as interferon, anti-PD-(L)-1, or anti-CTLA-4 will not count as a line of therapy as long as relapse did not occur during treatment or within 6 months of treatment discontinuation). • Must have progressed on treatment with an anti-PD-(L)1 mAb. PD-(L)1 treatment progression is defined as meeting all of the following criteria: - Has received at least 2 doses of an approved anti-PD-(L)1 mAb - Has demonstrated disease progression after PD-(L)1 as defined by RECIST v1.1. - Progressive disease has been documented within 12 weeks from the last dose of anti- PD-(L)1 mAb - Last dose of anti-PD-(L)1 must have been within 90 days prior to enrollment b. Cohort 2: Metastatic uveal melanoma • Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy • No prior regional, liver-directed therapy c. Cohort 3: Metastatic PD-(L)1-naïve melanoma • Uveal/ocular melanoma is excluded • Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy. • Participants with a targetable BRAF mutation, prior BRAF/MEK targeted therapy is allowed if completed 4 weeks prior to first dose of study treatment. d. Cohorts 4 and 5: Non-squamous NSCLC • Participants must have stage IV disease per American Joint Committee on Cancer (AJCC) 8th edition • No known driver mutations/alterations mutation for which targeted therapy is available • Must have non-squamous histology. • No prior therapy for metastatic disease • No prior treatment with anti-PD-(L)1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms 2. Able to provide archival tumor tissue from locations not radiated prior to biopsy. If archival tumor sample is not available, a fresh baseline biopsy is required. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 4. Measurable disease per RECIST v1.1 at baseline
Please refer to protocol for additional inclusion criteria. |
|
E.4 | Principal exclusion criteria |
1. History of another malignancy within 3 years of first dose of study drug 2. Active central nervous system (CNS) metastases and/or carcinomatous meningitis. 3. Previous exposure to CD40-targeted therapy 4. Currently on chronic systemic steroids in excess of physiologic replacement 5. Has had an allogeneic tissue/solid organ transplant. 6. History of autoimmune disease that has required systemic treatment in the past 2 years
Please refer to protocol for additional exclusion criteria. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Confirmed Objective Response Rate (ORR; confirmed complete response [CR] or partial response [PR]) according to RECIST v1.1 per investigator assessment. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Duration of treatment, approximately 2 years. |
|
E.5.2 | Secondary end point(s) |
- Type, incidence, severity, seriousness, and relatedness of adverse events (AEs). - Type, incidence, and severity of laboratory abnormalities. - Frequency of treatment interruptions, dose reductions, and treatment discontinuations due to AEs. - Disease control rate (DCR; confirmed CR, PR, and stable disease [SD]) per investigator assessment. - Duration of response (DOR; duration of confirmed CR or PR) per investigator assessment. - Progression-free survival (PFS) per investigator assessment. - Overall survival (OS). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- From start of treatment to 30-37 days after last dose, approximately 2 years. - From start of treatment to 30-37 days after last dose, approximately 2 years. - Duration of treatment, approximately 2 years. - From start of treatment until completion of response assessment, approximately 4 years. - From start of treatment until completion of response assessment, approximately 4 years. - From start of treatment until completion of response assessment, approximately 4 years. - Duration of study, approximately 4 years. |
|
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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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 | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Canada |
United Kingdom |
United States |
France |
Germany |
Spain |
Sweden |
|
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
|
The study will be closed 3 years after the last subject receives the last dose, or when no subjects remain in follow up, whichever occurs first. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 5 |