A Phase I/II study of DYP688 treatment alone in patients with eye cancer and other types of cancers of the skin and mucosal membranes in the body.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Nov 2022 → ongoing

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-509451-14-00

EudraCT number

2021-003380-95

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Pharmacodynamic, Efficacy, Safety

Phase I: to characterize the safety and tolerability and to identify the MTD and/or RD and regimen for future studies of DYP688 as a single agent.
Phase II: to evaluate the anti-tumor activity of DYP688 as a single agent.

Secondary objectives 8

1. Phase I •To characterize the pharmacokinetics (PK) of DYP688 as a single agent
2. Phase I •To assess the immunogenicity (IG) of DYP688 as a single agent
3. Phase I •To evaluate the preliminary anti-tumor activity of DYP688 as a single agent
4. Phase II •To further evaluate the anti-tumor activity of DYP688 as a single agent
5. Phase II •To evaluate the effects of DYP688 as a single agent on overall survival
6. Phase II •To further characterize the safety and tolerability of DYP688 as a single agent
7. Phase II •To further characterize the PK of DYP688 as a single agent
8. Phase II •To further characterize the IG of DYP688 as a single agent

Conditions and MedDRA coding

Metastatic uveal melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients in the dose escalation part must be ≥ 18 years of age at the time of informed consent (ICF) signature. In the phase II part, patients ≥ 12 years of age at the time of informed consent may be eligible for enrollment (not applicable in countries where enrollment is restricted by the local health authority to patients ≥ 18 years of age). Patients must have a minimum weight of 40 kg. For the 32 mg/kg dose level, a maximum weight limit of 115 kg may not be exceeded.
2. ECOG performance status ≤ 1 for patients ≥ 18 years of age; Karnofsky performance status ≥ 70 for patients ≥ 16 and < 18 years of age; Lansky performance status ≥ 70 for patients ≥ 12 and < 16 years of age.
3. Patients must be suitable and willing to undergo study required biopsies according to the treating institution's own guidelines and requirements, if medically feasible.
4. For all patients in Dose Escalation MUM: uveal melanoma with histologically or cytologically confirmed metastatic disease. Patient must be either treatment naive or have received any number of prior lines and progressed on most recent therapy.
5. For all patients in Dose Escalation Non-MUM: advanced cutaneous or mucosal melanoma with histologically or cytologically confirmed metastatic disease that has progressed following all standard therapies or that has no satisfactory alternative therapies and has evidence of GNAQ/11 mutation based on local data.
6. For patients in Phase II Tebentafusp naïve group: Diagnosis of uveal melanoma with histologically or cytologically confirmed metastatic disease that has progressed following standard therapies or that has no satisfactory alternative therapies.
7. For patients in Phase II Tebentafusp pre-treated group: Diagnosis of uveal melanoma with histologically or cytologically confirmed metastatic disease. Patients must be previously treated with tebentafusp and have progressed.
8. For patients in Phase II Non-MUM: patients with diagnosis of cutaneous or mucosal melanomas harboring GNAQ/11 mutations based on local data, with histologically or cytologically confirmed metastatic disease that has progressed following all standard therapies or that has no satisfactory alternative therapies.

Exclusion criteria 6

1. Malignant disease, other than that being treated in this study.
2. Active brain metastases, i.e. symptomatic brain metastases or known leptomeningeal disease.
3. Evidence of active bleeding or bleeding diathesis or significant coagulopathy (including familial) or a medical condition requiring long term systemic anticoagulation that would interfere with biopsies.
4. History of anaphylactic or other severe hypersensitivity / infusion reactions to ADCs or monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
5. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes: •≤ 2 weeks for fluoropyrimidine therapy •≤ 4 weeks for radiation therapy or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment. •≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent. •≤ 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosoureas and mitomycin C. •≤ 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PDL1 antagonists.
6. Clinically significant and / or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2) or clinically significant arrhythmia despite medical treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Phase I: Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.
2. Phase I: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, electrocardiograms (ECGs), and vital signs.
3. Phase I: Frequency of dose interruptions, reductions, and discontinuations.
4. Phase II: Overall Response rate (ORR) per RECIST 1.1.

Secondary endpoints 9

1. Phase I and Phase II: PK parameters for total mAb, conjugated active and inactive payload, and unconjugated active payloads (e.g., AUC, Cmax, CL, half-life).
2. Phase I: Prevalence and incidence of anti-DYP688 antibodies.
3. Phase I: Best Overall Response (BOR).
4. Phase I: Overall Response Rate (ORR) per RECIST v1.1.
5. Phase II: Duration of response (DoR), progression free survival (PFS) and DCR per RECIST v1.1.
6. Phase II: Overall survival (OS)
7. Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, electrocardiograms (ECGs), and vital signs.
8. Phase II: Frequency of dose interruptions, reductions, and discontinuations PK parameters for total mAb, conjugated active and inactive payload, and unconjugated active payloads (e.g., AUC, Cmax, CL, half-life).
9. Phase II: Prevalence and incidence of anti-DYP688 antibodies.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 14

Locations

4 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications