A Phase 1 Study of Sigvotatug Vedotin in Advanced Solid Tumors

Plain English Summary

A Study of Sigvotatug Vedotin in Advanced Solid Tumors is a Phase 1 clinical trial sponsored by Seagen, a wholly owned subsidiary of Pfizer studying Carcinoma, Non-Small Cell Lung, Squamous Cell Carcinoma of Head and Neck, HER2 Negative Breast Neoplasms, Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Ovarian Neoplasms, Cutaneous Squamous Cell Cancer, Exocrine Pancreatic Adenocarcinoma, Urinary Bladder Neoplasms. This trial tests a new drug, sigvotatug vedotin, alone or with other cancer treatments, to see if it's safe and effective for advanced solid tumors. It is for adults with specific types of advanced solid tumors that have not responded to or cannot be treated with standard therapies. Participation involves receiving the study drug(s) through an IV, with regular check-ups and tests to monitor safety and response. Alternative treatments may include standard chemotherapy, targeted therapies, or immunotherapy, depending on the specific cancer type and prior treatments. The trial aims to enroll 1006 participants.

Official Summary

This trial will look at a drug called sigvotatug vedotin (SGN-B6A) alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe for people who have solid tumors. It will study sigvotatug vedotin to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study whether sigvotatug vedotin works to treat solid tumors. The study will have four parts. * Part A of the study will find out how much sigvotatug vedotin should be given to participants. * Part B will use the dose found in Part A to find out how safe sigvotatug vedotin is and if it works to treat solid tumors. * Part C of the study will find out how safe sigvotatug vedotin is in combination with these other drugs. * Part D will include people who have not received treatment. This part of the study will find out how safe sigvotatug vedotin is in combination with these other drugs and if these combinations work to treat solid tumors. * In Parts C and D, participants will receive sigvotatug vedotin with either: * Pembrolizumab or, * Pembrolizumab and carboplatin, or * Pembrolizumab and cisplatin.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with specific types of advanced solid tumors, including lung, head and neck, breast, esophageal, pancreatic, bladder, cervical, gastric, and ovarian cancers. Patients must have disease that is relapsed, refractory, or intolerant to standard treatments, and may need to have received prior platinum-based therapy and PD-1/PD-(L)1 inhibitors depending on the study part. Participants must have a good general health status (ECOG performance status of 0 or 1) and measurable disease. Individuals with active brain metastases, certain prior cancer treatments (e.g., MMAE-containing agents), or significant lung disease may not be eligible. This trial is studying Carcinoma, Non-Small Cell Lung, Squamous Cell Carcinoma of Head and Neck, HER2 Negative Breast Neoplasms, Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Ovarian Neoplasms, Cutaneous Squamous Cell Cancer, Exocrine Pancreatic Adenocarcinoma, Urinary Bladder Neoplasms, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure the frequency and severity of side effects and dose-limiting toxicities, which helps determine the safe dosage and tolerability of sigvotatug vedotin for patients. The specific primary outcome measures are: Number of participants with adverse events (AEs) (Through 30-37 days following last dose of sigvotatug vedotin. For participants receiving pembrolizumab up to 90 days after last dose of pembrolizumab; up to 3 years); Number of patients with laboratory abnormalities (Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years); Number of participants with dose-limiting toxicities (DLTs) (Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a need for new treatments in advanced solid tumors by investigating sigvotatug vedotin, a novel drug, which may offer a new option for patients with limited treatment choices. This research targets Carcinoma, Non-Small Cell Lung, Squamous Cell Carcinoma of Head and Neck, HER2 Negative Breast Neoplasms, Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Ovarian Neoplasms, Cutaneous Squamous Cell Cancer, Exocrine Pancreatic Adenocarcinoma, Urinary Bladder Neoplasms, where improved treatment options are needed.

Investor Insight

This Phase 1 trial, sponsored by Seagen (a Pfizer subsidiary), is exploring a novel drug in a large patient population with advanced solid tumors, indicating potential for a significant market if succ Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval. The large enrollment target of 1006 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific drugs being tested, how they are given, and what side effects are most common. Understand the schedule of visits, tests (including biopsies), and potential hospital stays required for the trial. Discuss how this trial fits with other treatment options and what happens if the treatment doesn't work or causes significant side effects. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 1,006 participants

Interventions

• DRUG: sigvotatug vedotin — Administered into the vein (IV; intravenously)
• DRUG: pembrolizumab — 200mg every 3 weeks or 400mg every 6 weeks, given by IV
• DRUG: cisplatin — 75 mg/m2 every 3 weeks, given by IV
• DRUG: carboplatin — AUC 5 mg/mL per min every 3 weeks, given by IV

Primary Outcomes

• Number of participants with adverse events (AEs) (Through 30-37 days following last dose of sigvotatug vedotin. For participants receiving pembrolizumab up to 90 days after last dose of pembrolizumab; up to 3 years)
• Number of patients with laboratory abnormalities (Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)
• Number of participants with dose-limiting toxicities (DLTs) (Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)

Secondary Outcomes

• Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment (Up to approximately 3 years)
• Duration of objective response (DOR) per RECIST v1.1 by investigator assessment (Up to approximately 3 years)
• Progression-free survival (PFS) per RECIST v1.1 by investigator assessment (Up to approximately 3 years)
• Overall survival (OS) (Up to approximately 3 years)
• Area under the concentration-time curve (AUC) (Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years)

Full Eligibility Criteria

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 naïve for locally advanced or metastatic systemic therapy (prior definitively intended or \[neo\]adjuvant therapy is allowed).
  * Part D only: Participants must be treatment naïve 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.

Trial Locations

• Alaska Oncology and Hematology, Anchorage, Alaska, United States
• Highlands Oncology Group, Fayetteville, Arkansas, United States
• Highlands Oncology Group, Rogers, Arkansas, United States
• Highlands Oncology Group, Springdale, Arkansas, United States
• Providence Medical Foundation, Anaheim, California, United States
• Providence Medical Foundation, Fullerton, California, United States
• Providence St. Jude Medical Center Virginia K Crosson and Infusion Center, Fullerton, California, United States
• Cancer and Blood Research Center, LLC, Los Alamitos, California, United States
• Cancer and Blood Specialty Clinic, Los Alamitos, California, United States
• Ronald Reagan UCLA Medical Center, Los Angeles, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• Head and Neck Squamous Cell Carcinoma
• Breast Cancer (HER2-negative)
• Esophageal Squamous Cell Carcinoma
• Esophageal Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Ovarian Neoplasms
• Cutaneous Squamous Cell Cancer
• Exocrine Pancreatic Adenocarcinoma
• Urinary Bladder Neoplasms

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