Study of GVV858 as a single agent or in combination with endocrine therapy in patients with HR+/HER2- breast cancer and other advanced solid tumors

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

26 May 2026 → ongoing

Decision date (initial)

2026-04-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2025-521911-38-00

WHO UTN

U1111-1333-0414

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Others, Pharmacodynamic, Pharmacokinetic, Safety

Phase I:

To assess the safety and tolerability of GVV858 as a single agent and in combination with fulvestrant or letrozole.

To identify the recommended dose(s) (RD) and/or dose range for optimization (DRO) for further clinical evaluation.

Phase II:

To further characterize the safety and tolerability of GVV858 in combination with fulvestrant.

Secondary objectives 2

1. Phase I: To characterize the PK of GV858 (both as a single agent and in combination with fulvestrant or letrozole). To evaluate preliminary anti-tumor activity of GVV858 as a single agent and in combination with fulvestrant or letrozole.
2. Phase II: To further evaluate preliminary anti-tumor activity of GVV858 in combination with fulvestrant. To further characterize the PK of GVV858 in combination with fulvestrant.

Conditions and MedDRA coding

Advanced HR+/HER- breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 years old.
2. Phase I, Dose escalation: Patients with one of the following histologically or cytologically confirmed advanced cancers, for whom no standard therapy is available or appropriate in the judgement of the investigator: HR+/HER2- advanced breast cancer (aBC) with disease progression on or following, or have been intolerant to, at least one line of hormone-based therapy in combination with a CDK4/6i for advanced disease (or during or within 12 months of completing adjuvant endocrine therapy (ET) plus CDK4/6i therapy), and at least one additional line of systemic therapy for metastatic disease. Locally advanced or metastatic solid malignancy with CCNE-1 amplification.
3. Phase I, Dose expansion: Patients with one of the following histologically or cytologically confirmed advanced cancers, for whom no standard therapy is available or appropriate in the judgement of the investigator: HR+/HER2- aBC with disease progression on or following, or have been intolerant to, at least one line of hormone-based therapy in combination with a CDK4/6i for advanced disease (or during or within 12 months of completing adjuvant ET plus CDK4/6i therapy), and at least one additional line of systemic therapy for metastatic disease. Advanced or metastatic ovarian cancer (OC) with CCNE-1 amplification, following progression on or after, or intolerance to, standard-of-care (SOC) therapy. Advanced or metastatic gastric or esophageal adenocarcinoma (GEA) with CCNE-1 amplification, following progression on or after, or intolerance to, SOC therapy. Metastatic castration-resistant prostate cancer (mCRPC) with disease progression on or after, or intolerance to, at least one line of androgen receptor pathway inhibitor therapy (ARPI) and at least one line of taxane-based chemotherapy, and no more than 3 total prior lines of systemic therapy for metastatic disease.
4. Phase II: HR+/HER2- a BC with disease progression on or after an endocrine therapy in combination with a CDK4/6 inhibitor for advanced disease, with no more than 2 total lines of endocrine therapy for advanced disease, and no prior cytotoxic chemotherapy or antibody-drug conjugate therapy for advanced disease.
5. Measurable disease as determined by RECIST v1.1, with the following exceptions: aBC only: If no measurable disease is present, then at least one predominantly lytic bone lesion must be present that can be accurately assessed at baseline and is suitable for repeated assessment. mCRPC only: If no measurable disease is present per PCWG3 modified RECIST, then at least one metastatic lesion must be present on bone scan imaging obtained prior to C1D1.

Exclusion criteria 6

1. Patients with inadequate bone marrow and/or organ function.
2. Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local therapy or increasing doses of corticosteroids within 2 weeks prior to study entry.
3. Patients with symptomatic visceral disease, including visceral crisis.
4. For patients with breast cancer only: Patient is concurrently using hormone replacement therapy. Pre/perimenopausal women or men with breast cancer who are unwilling or unable to be treated with a Luteinizing Hormone-Releasing Hormone (LHRH) agonist (goserelin or leuprolide) for gonadal suppression, as per locally approved label (see Protocol Section 6.1.1).
5. Women of childbearing potential (WOCBP) who are unwilling to use highly effective contraception methods.
6. Pregnant or nursing women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I: Safety: Incidence and severity of dose-limiting toxicities (DLTs), adverse events (AEs) and serious adverse events (SAEs), including changes in lab values, vital signs, electrocardiograms (ECGs). Tolerability: Frequency of dose interruptions, reductions, discontinuations, dose intensity.
2. Phase II: Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in lab values, vital signs, electrocardiograms (ECGs). Tolerability: Frequency of dose interruptions, reductions, discontinuations, dose intensity.

Secondary endpoints 2

1. Phase II: ORR, BOR, DCR, CBR, PFS and duration of response (DOR) per investigator assessment of RECIST v1.1. Plasma concentrations of GVV858 and derived PK parameters (e.g., AUC, Tmax, and Cmax).
2. Phase I: Plasma concentrations of GVV858 and derived PK parameters (e.g., AUC, Tmax, Cmax). ORR, BOR, DCR, CBR, and PFS per investigator assessment of response evaluation criteria in solid tumors (RECIST v1.1), or local PCWG3 criteria including PCWG3-modified RECIST v1.1 (prostate cancer patients only).

Investigational products

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

Test 4

Auxiliary 4

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

6 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 56 files

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

Application history

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