A Study of Disitamab Vedotin with Other Anticancer Drugs in Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seagen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Aug 2024 → ongoing

Decision date (initial)

2024-06-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

• To identify the maximum tolerated dose (MTD) and/or optimal dose of disitamab vedotin when administered in combination with tucatinib.
• To characterize the safety and tolerability of disitamab vedotin plus tucatinib in:
◦ HER2-low second-line (2L) or third-line (3L) advanced BC
◦ HER2+ 3L+ advanced BC
◦ HER2-low 2L advanced GC/GEJC
◦ HER2+ 2L or 3L advanced GC/GEJC
● To assess the antitumor activity of disitamab vedotin plus tucatinib in:
◦ HER2-low 2L or 3L advanced BC
◦ HER2+ 3L+ advanced BC
◦ HER2-low 2L advanced GC/GEJC
◦ HER2+ 2L or 3L advanced GC/GEJC

Secondary objectives 3

1. To assess the antitumor activity of disitamab vedotin plus tucatinib
2. To characterize the pharmacokinetics (PK) of disitamab vedotin plus tucatinib, total antibody, and unconjugated monomethyl auristatin E (MMAE)
3. To characterize the immunogenicity of disitamab vedotin

Conditions and MedDRA coding

LA/mGC/GEJC (locally advanced unresectable or metastatic gastric cancer and gastroesophageal junction adenocarcinoma, collectively) and LA/mBC (locally advanced metastatic breast cancer)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically or cytologically confirmed diagnosis of breast carcinoma or gastric or gastroesophageal junction adenocarcinoma
2. HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/in situ hybridization (ISH)-negative) based on American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) guidelines for assessment of HER2 in BC for interpretation of HER2 expression and amplification or must have HER2-low expression defined as IHC 1+ or IHC 2+/ISH-negative determined by most recent local assessment based off the ASCO and CAP guidelines for assessment of HER2 in gastric cancer (GC) for interpretation of HER2 expression and amplification. -or-
3. HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+) according to ASCO and CAP guidelines for assessment of HER2 in BC or GC/GEJC
4. Prior therapies requirements: In HER2-Low Breast Cancer participants: a. No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC. Participants previously treated with (neo)adjuvant cytotoxic chemotherapy and have disease relapsed within 6 month of treatment is considered to have received 1 line of cytotoxic therapy for LA/mBC. b. Participants with known germline BRCA mutation must have received a PARP-inhibitor, where available and not medically contraindicated c. Have progression on or after, or be intolerant to, trastuzumab deruxtecan (T-DXd) d. Participants with hormone receptor-positive (HR+) tumors must have intolerance to endocrine therapy or endocrine therapy refractory disease: i. Progressed on ≥2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting if available as local standard of care and not contraindicated OR ii. Progressed on 1 line of endocrine therapy for LA/mBC AND had a relapse while on adjuvant endocrine therapy after definitive surgery for primary tumor AND had received a CDK4/6 inhibitor in the adjuvant or advanced setting if available as local standard of care and not contraindicated iii. Note that prior endocrine and CDK4/6 inhibitor therapy for low ER and PR expression (immunohistochemical staining of only 1 to 10% of tumor cells) is per institutional standard and not mandated prior to enrollment iv. Participants with HR+ HER2-low tumors must have progression on or after, or be intolerant to, prior cytotoxic chemotherapy (including ADCs) if available as local standard of care for endocrine therapy refractory advanced disease. e. Participants with hormone receptor (HR) negative, HER2-low and programmed cell death receptor ligand 1 (PD-L1)-positive tumors must have received pembrolizumab (or other PD-(L)1 inhibitor) with chemotherapy if available as local standard of care therapy and not medically contraindicated. In HER2+ Breast Cancer participants: a. Received first line standard of care therapy for advanced disease (e.g. trastuzumab, pertuzumab and a taxane or T-DXd based therapy). b. Have progression on or after, or be intolerant to, T-DXd c. No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC
5. All participants in: HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma must have: a. Prior systemic therapy with platinum, fluorouracil, or taxane for locally advanced unresectable or metastatic disease b. Progression within 6 months of last dose of (neo)adjuvant cytotoxic chemotherapy is considered as 1 line of systemic therapy for LA/mGC/GEJC c. Prior anti-PD-(L)1 (programmed cell death receptor 1 [PD1] and PD-L1, collectively) therapy is allowed d. No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADC) for LA/mGC/GEJC HER2+ LA/m Gastric or Gastroesophageal Junction Adenocarcinoma must have: a. Received prior trastuzumab plus fluoropyrimidine and platinum containing chemotherapy if no contraindication. b. Prior T-DXd treatment is allowed c. Prior PD1 inhibitor therapy is allowed d. No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mGC/GEJC.
6. Note that gastric cancer cohorts are closed for enrollment. There are no LA/mGC/GEJC participants in the dose optimization and expansion phases.

Exclusion criteria 6

1. Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib
2. Prior therapy with ADCs with MMAE payload
3. Prior therapy with tucatinib
4. Participants who have received prior systemic anticancer treatment including investigational agents within 4 weeks, or 5 half-lives, whichever is shorter, prior to first dose of study treatment.
5. Participants with a history of other invasive malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
6. Participants who have received prior radiotherapy within 2 weeks of start of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Incidence of dose-limiting toxicities (DLTs) in dose escalation phase
2. Type, incidence, severity, seriousness, and relatedness of AEs
3. Type, incidence, and severity of laboratory abnormalities as well as significant changes from baseline
4. Frequency of treatment interruptions, dose reductions, and treatment discontinuations due to AEs
5. ORR (confirmed complete response [CR] and confirmed partial response [PR]) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment

Secondary endpoints 6

1. Duration of response (DOR) per RECIST v1.1 by investigator assessment
2. Disease control rate (DCR) (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1 by investigator assessment
3. Progression-free survival (PFS) per RECIST v1.1 by investigator assessment
4. Overall Survival (OS)
5. Estimates of selected PK parameters of disitamab vedotin, total antibody, and unconjugated MMAE
6. Incidence of anti-drug antibodies (ADA) against disitamab vedotin

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seagen Inc.

Sponsor organisation

Seagen Inc.

Address

21823 30th Drive Southeast

City

Bothell

Postcode

98021-3907

Country

United States

Scientific contact point

Organisation

Seagen Inc.

Contact name

Seagen Clinical Trial Information Support

Public contact point

Organisation

Seagen Inc.

Contact name

Seagen Clinical Trial Information Support

Third parties 11

Locations

4 EU/EEA countries · 20 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 31 files

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

Application history

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