Phase 1 study of SGN-B6A in advanced solid tumors
Résumé de l'étude
This is a multicenter study conducted in Switzerland, other European countries, and the United States. In this study, we will evaluate the investigational drug SGN-B6A for the first time in humans with advanced solid tumors. We will test the investigational drug SGN-B6A alone, in combination with pembrolizumab (brand name KEYTRUDA®), and in combination with pembrolizumab and chemotherapy (cisplatin or carboplatin) to determine if it is safe, what its side effects are, and whether it works for advanced solid tumors. Cisplatin and carboplatin are chemotherapy drugs approved by the EMA and in Switzerland by Swissmedic for the treatment of several types of cancer. Both cisplatin and carboplatin use platinum to combat tumor cells. Thousands of cancer patients have already received cisplatin and carboplatin. This is an open-label study, meaning that the study doctor and the patient know which of the investigational drugs will be administered. The duration of participation in the study is not defined as it will depend on how the patient's body reacts to the investigational drug and the results observed in other study participants. Patients may continue to receive SGN-B6A alone as long as the cancer remains stable or improves, or until the study ends. Patients may receive pembrolizumab for about 2 years. You may receive cisplatin or carboplatin for a maximum of 6 cycles.
(BASEC)
Intervention étudiée
Patients in the SGN-B6A alone arm and patients in the SGN-B6A arm with pembrolizumab or with pembrolizumab and cisplatin or carboplatin will receive the investigational drugs intravenously according to 4 different schedules at the study site. Each study period, referred to as a "cycle," lasts approximately 3 or 4 weeks. To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of SGN-B6A alone, in combination with pembrolizumab or with pembrolizumab and cisplatin or carboplatin, blood samples will be collected up to 12 times per cycle for laboratory assessments. A tumor sample will be collected during the selection period. ECGs and physical examinations are performed regularly. CT scans and/or MRIs will be performed every 6 weeks until week 16, then every 9 weeks thereafter if you are on a 3-week cycle or every 6 weeks until week 24, then every 8 weeks thereafter if you are on a 4-week cycle. In addition to the evaluation of biological samples and images, patients will be asked to complete various questionnaires, and those who wish may participate in telephone interviews to share their personal experiences of participating in the study.
(BASEC)
Maladie en cours d'investigation
Metastatic or unresectable solid tumors.
(BASEC)
1. Patients with one of the following types of cancer that have not improved or have recurred after the last treatment may participate: - Non-small cell lung cancer - Head and neck cancer - Breast cancer - Squamous cell carcinoma of the esophagus - Ovarian cancer - Esophageal adenocarcinoma/gastroesophageal adenocarcinoma - Skin cancer - Pancreatic cancer - Bladder cancer - Cervical cancer - Stomach cancer 2. Tumor site accessible for biopsy 3. Age 18 years or older 4. Women of childbearing potential and men capable of fathering children must commit to using strict contraceptive measures. 5. Laboratory values must meet the eligibility criteria specified in the protocol. (BASEC)
Critères d'exclusion
1. History of another malignant tumor within 3 years prior to the first dose of the investigational drug, or any signs of residual disease from a previously diagnosed malignant tumor 2. Known active metastases to the central nervous system 3. Carcinomatous meningitis 4. Prior receipt of a specific drug 5. Pre-existing neuropathy ≥ Grade 2 6. Any uncontrolled viral, bacterial, or fungal infection in the 2 weeks prior to the first dose of SGN-B6A. 7. Uncontrolled diabetes mellitus 8. Positive for active hepatitis B or hepatitis C 9. Known to be HIV positive 10. History of cerebrovascular event in the last 6 months 11. Congestive heart failure Class III or IV (BASEC)
Lieu de l’étude
Chur, Lausanne
(BASEC)
Sponsor
Seagen Inc., (A wholly owned subsidiary of Pfizer Inc.), 21823 30th Drive SE, Bothell, WA 98021, United States
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Ms. Alessandra Fedato
+41 763885296
alessandra.fedato@clutterpfizer.comPfizer AG, Schärenmoosstrasse 99, 8052, Zürich, Switzerland
(BASEC)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique du Vaud
(BASEC)
Date d'approbation du comité d'éthique
10.06.2021
(BASEC)
Identifiant de l'essai ICTRP
NCT04389632 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
A Phase 1 Study of SGN-B6A in Advanced Solid Tumors (BASEC)
Titre académique
A Phase 1 Study of Sigvotatug Vedotin in Advanced Solid Tumors (ICTRP)
Titre public
A Study of Sigvotatug Vedotin in Advanced Solid Tumors (ICTRP)
Maladie en cours d'investigation
Carcinoma, Non-Small Cell LungSquamous Cell Carcinoma of Head and NeckHER2 Negative Breast NeoplasmsEsophageal Squamous Cell CarcinomaEsophageal AdenocarcinomaGastroesophageal Junction AdenocarcinomaOvarian NeoplasmsCutaneous Squamous Cell CancerExocrine Pancreatic AdenocarcinomaUrinary Bladder NeoplasmsUterine Cervical NeoplasmsStomach Neoplasms (ICTRP)
Intervention étudiée
Drug: sigvotatug vedotinDrug: pembrolizumabDrug: cisplatinDrug: carboplatin (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: N/A. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
- Disease indication
- Participants must have histologically or cytologically confirmed metastatic or
unresectable solid malignancy within one of the tumor types listed below
(dependent on study part).
- Non-small cell lung cancer (NSCLC)
- Head and neck squamous cell cancer (HNSCC)
- Advanced HER2-negative breast cancer
- Esophageal squamous cell carcinoma (ESCC)
- Esophageal/Gastro-esophageal junction adenocarcinoma (EAC/GEJ)
- Cutaneous squamous cell cancer (cSCC)
- Exocrine pancreatic adenocarcinoma
- Bladder cancer
- Cervical cancer
- Gastric cancer
- High grade serous ovarian cancer (HGSOC)
- Part A only: Participants must have disease that is relapsed or refractory or
be intolerant to standard-of-care therapies and should have no appropriate
standard-of-care therapeutic options.
- Part B only: Participants must have disease that is relapsed or refractory or
be intolerant to standard-of-care therapies. Participants must have received
platinum-based therapy and a PD-1/PD-(L)1 inhibitor, if applicable and
available.
- Part C only: For pembrolizumab combination cohorts, participants must be
eligible for pembrolizumab per local standard of care. For pembrolizumab with
cisplatin or carboplatin, participants must be eligible for both pembrolizumab
and the platinum agent per local standard of care. Participants must be
treatment nave for locally advanced or metastatic systemic therapy (prior
definitively intended or [neo]adjuvant therapy is allowed).
- Part D only: Participants must be treatment nave for locally advanced or
metastatic systemic therapy.
- Participants enrolled in the following study parts should have a tumor site
accessible for biopsy and agree to biopsy as follows:
- Disease-specific expansion cohorts (Part B and Part D): A baseline fresh tumor
biopsy is required. An archival biopsy collected within 90 days prior to first
dose of study drug may be used.
- Biology expansion cohort: pretreatment biopsy and on-treatment (Cycle 1) biopsy
- An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Measurable disease per the RECIST v1.1 at baseline
Exclusion Criteria
- History of another malignancy within 3 years before first dose of study drug, or any
evidence of residual disease from a previously diagnosed malignancy. Exceptions are
malignancies with a negligible risk of metastasis or death.
- Known active central nervous system metastases. Participants with previously treated
brain metastases may participate provided they:
- are clinically stable for at least 4 weeks prior to study entry after brain
metastasis treatment,
- have no new or enlarging brain metastases, and
- are off of corticosteroids prescribed for symptoms associated with brain
metastases for at least 7 days prior to first dose of study drug.
- In Part D, participants with untreated, asymptomatic CNS metastases smaller
than 1 cm may be enrolled without definitive treatment as long as they have no
neurological symptoms, no or minimal surrounding edema, and no requirements for
corticosteroids.
- Carcinomatous meningitis
- Previous receipt of an MMAE-containing agent or an agent targeting integrin beta-6
- Pre-existing neuropathy Grade 1 or greater per the National Cancer Institute's
Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) for
Parts C and D cohorts with cisplatin or carboplatin Grade 2 or greater per the NCI
CTCAE v5.0 for all other cohorts
- Any uncontrolled Grade 3 or higher (per NCI CTCAE v5.0) viral, bacterial, or fungal
infection within 2 weeks prior to the first dose of sigvotatug vedotin.
- Routine antimicrobial prophylaxis is permitted
- Grade =3 pulmonary disease unrelated to underlying malignancy. This includes
clinically severe pulmonary function compromise resulting from clinically
significant pulmonary illnesses
- Part C and D: Prior therapy with a PD-1 inhibitor, anti-PD-(L)1, or anti PD-L2 agent
or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
and was discontinued from that treatment due to a Grade 3 or higher immune-mediated
adverse event (IMAE).
- History of noninfectious interstitial lung disease (ILD) or pneumonitis that
required steroids, current ILD or pneumonitis, or suspected ILD or pneumonitis that
cannot be ruled out by imaging at screening
- Known diffusing capacity of the lung for carbon monoxide (DLCO adjusted for
hemoglobin) <50% predicted
- Investigator site staff directly involved in the conduct of the study and their
family members, site staff otherwise supervised by the investigator, and sponsor and
sponsor delegate employees directly involved in the conduct of the study and their
family members. (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Number of participants with adverse events (AEs);Number of patients with laboratory abnormalities;Number of participants with dose-limiting toxicities (DLTs) (ICTRP)
Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment;Duration of objective response (DOR) per RECIST v1.1 by investigator assessment;Progression-free survival (PFS) per RECIST v1.1 by investigator assessment;Overall survival (OS);Area under the concentration-time curve (AUC);Concentration at the end of infusion (Ceoi);Maximum observed concentration (Cmax);Time to maximum observed concentration (Tmax);Trough concentration (Ctrough);Apparent terminal elimination half-life (t1/2);Number of participants with antidrug antibodies (ADAs) (ICTRP)
Date d'enregistrement
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Inclusion du premier participant
non disponible
Sponsors secondaires
non disponible
Contacts supplémentaires
Medical Monitor;Seagen Trial Information Support, clinicaltrials@seagen.com, 866-333-7436, Seagen Inc., (ICTRP)
ID secondaires
C5751001, 2023-508469-34-00, SGNB6A-001 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT04389632 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
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