E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028997 |
E.1.2 | Term | Neoplasm malignant |
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 A (not conducted in EU): • To assess the safety and tolerability of NM21-1480 • To determine the maximum tolerated dose (MTD) of NM21-1480 • To determine up to four (4) safe dose levels for further evaluation of pharmacodynamics (PD) and clinical activity in the optional Part A-2 and Part B of the study
Part A-2 (OPTIONAL - not conducted in EU): • To assess the safety and tolerability of NM21-1480 • To further characterize PD response at or below the MTD in support of selection of up to four (4) safe dose levels to be further studied in Part B
Part B: • To determine the anti-tumor activity of NM21-1480 according to RECIST 1.1 • To assess the safety and tolerability of NM21-1480 in patients with selected advanced cancers • To determine the recommended Phase 2 dose (RP2D) • To determine the safety and efficacy of NM21-1480 in combination with standard-of-care anti-PD1 therapy in patients with head and neck squamous cell cancer (Cohort B5) |
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E.2.2 | Secondary objectives of the trial |
Part A (not conducted in EU): • To characterize the pharmacokinetics (PK) profile of NM21-1480 • To evaluate the immunogenicity of NM21-1480
Part A-2 (OPTIONAL - (not conducted in EU): • To characterize the PK profile of NM21-1480 • To evaluate the immunogenicity of NM21-1480
Part B: • To further evaluate the preliminary anti-tumor activity of NM21-1480 • To characterize the PK profile of NM21-1480 • To evaluate the immunogenicity of NM21-1480 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Parts A and A-2 are not conducted in EU/EEA and, therefore, specific inclusion criteria are not described.
Part B: • Patients with Non-small Cell Lung Cancer (NSCLC) or other protocol-specified solid tumors with locally advanced or metastatic, non-resectable disease, which has progressed despite treatment with first-line standard-of-care treatment, or first- and second-line treatment, dependent on expansion cohort. • Prior therapy must have been completed 2-4 weeks prior to the administration of the first dose of study drug as specified per protocol according to type of prior therapy.
Part B: (all cohorts): Patients with locally advanced or metastatic, nonresectable disease per cohort specific criteria listed in the protocol: • Cohorts B1, B3, and B7 o Patients with NSCLC
•Cohort B2 o Patients with HPV-associated (i.e. HPV+ tumor) SCC of the anus, cervix, vulva, vagina, penis or oropharynx
•Cohort B4 o Patients with recurrent, persistent or metastatic ovarian, primary peritoneal or fallopian tumor carcinoma
•Cohort B5 o Patients with head and neck squamous cell cancer
•Cohort B6: o Patients with measureable TNBC |
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E.4 | Principal exclusion criteria |
•Previous immediate or delayed hypersensitivity reaction or idiosyncrasy to the excipients. •Active or prior autoimmune disease, with the following allowed exceptions: o Vitiligo, autoimmune thyroiditis, or psoriasis (not requiring systemic treatment within 2 years), type I diabetes on stable insulin therapy or – in the view of the Investigator – resolved childhood asthma/atopy; o Intermittent use of bronchodilators, inhaled steroids or local steroid injections including intra-articular injections; o Hypothyroidism stabilized on HRT; and o Celiac disease adequately controlled by diet alone.
Parts A and A-2 are not conducted in EU/EEA and, therefore, specific exclusion criteria are not described.
Part B: •Cohort B1 and B7: o Treatment other than anti-PD-1 and/or chemotherapy prior to treatment initiation or not recovered to CTCAE V5.0 Grade 1 or better from AE due to prior anti-PD-1 administration •Cohort B2: o Treatment other than anti-PD-1 or a platinum-based chemotherapy regimen recommended as first-line or second-line treatment by current NCCN treatment guidelines or not recovered to CTCAE V5.0 Grade 1 or better from AE due to first- or second-line treatment. •Cohort B3: o Any treatment other than a local standard-of-care first-line chemotherapy regimen or not recovered to CTCAE V5.0 Grade 1 or better from AE due to first-line treatment. o Receipt of a PD-1, PD-L1, 4-1BB or CTLA-4 antibody or any other investigational biological drugs. o EGFR tyrosine kinase activating mutations or ALK gene rearrangements. •Cohort B4: o Prior therapy with anti-PD-1, anti-PD-L1, anti-4-1BB or anti-CTLA-4 antibodies or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways. o Prior chemotherapy for any abdominal or pelvic tumor other than ovarian, fallopian tube, or primary peritoneal cancer within 3 years •Cohort B5: o Previous systemic drug therapy for their disease. •Cohort B6: o For subgroup 1: -Treatment with PD-1 or PD-L1 antibody within 2 weeks or 5 half-lives of first dose of study drug, respectively. -Has not recovered to CTCAE V5.0 Grade 1 or better from AE due to prior anti-PD-1 or anti-PD-1 antibody. -Previous treatment with anti-CTLA-4 or anti-4-1BB antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways other than the PD-1/PD-L1 pathway o For subgroup 2: -Prior therapy with anti-PD-1, anti-PD-L1, anti-4-1BB or anti-CTLA-4 antibodies or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A (not conducted in EU): • Incidence and nature of dose-limiting toxicities (DLTs) • Incidence and severity of treatment-emergent adverse events (TEAEs) with specific focus on incidence and severity of immune-related adverse events (irAEs)
Part A-2 (OPTIONAL - not conducted in EU): • Incidence and severity of TEAEs with specific focus on incidence and severity of irAEs • Characterization of exposure-dependent PD markers of target and pathway engagement.
Part B: • Best overall response (BOR) (Primary endpoint for Cohort B1-4, 6-7) • Objective response rate (ORR) (Primary endpoint for Cohort B5) • Incidence and severity of TEAEs with specific focus on incidence and severity of irAEs • Characterization of exposure-dependent PD markers of target and pathway engagement. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DLTs - up to 28 days fro the first dose of study drug TEAEs - from the time of informed consent through 70 days after the administration of the last dose of study drug. PD markers - Cycle 1 Days 1 and 15, Cycle 2, Days 29 and 43, Cycle 3 Day 57 and every subsequent odd numbered cycle BOR, ORR - from the first dose of study drug until documented disease progression |
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E.5.2 | Secondary end point(s) |
Part A (not conducted in EU): • PK parameters: AUCtau, AUC (0-infinity) (first dose only), Cmax, Cmin, t½, Tmax, λz, CL, Vd • Frequency of specific anti-drug antibodies to NM21-1480
Part A-2 (OPTIONAL - not conducted in EU): • PK parameters: AUCtau, AUC (0-infinity) (first dose only), Cmax, Cmin, t½, Tmax, λz, CL, Vd • Frequency of specific anti-drug antibodies to NM21-1480
Part B: • Disease Control Rate (DCR) according to RECIST1.1 • Duration of Response (DOR) according to RECIST1.1 • Progression-free survival (PFS) according to RECIST1.1 • Overall survival (OS) • BOR, DCR, ORR, DOR, and PFS as per iRECIST • PK parameters: AUCtau, AUC (0-infinity) (first dose only), Cmax, Cmin, t½, Tmax, λz, CL, Vd • Frequency of specific anti-drug antibodies (ADAs) to NM21-1480 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK and ADA - Cycle 1 Days 1 and 15, Cycle 2, Days 29 and 43, Cycle 3 Day 57 and every subsequent odd numbered cycle DOR - from first radiographic evidence of response to the earliest documented disease progression or death. PFS, BOR, ORR, DCR - from start of study treatment to the earliest documented date of disease progression. OS - from start of study treatment to death due to any cause. |
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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 | Yes |
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 |
Tolerability, Immunogenicity |
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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 |
Dose escalation and dose expansion (first administration to humans phase completed) |
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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 | 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 | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 26 |
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 |
Georgia |
Germany |
Netherlands |
Spain |
Taiwan |
Turkey |
Ukraine |
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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The end of the study is defined as the date once all patients have completed the Follow-up period (i.e., 12 weeks after discontinuation). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 14 |