SGN-35C for Lymphoma

Recruiting in Palo Alto (17 mi)

+41 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Seagen Inc.

Must not be taking: Antibody-drug conjugates

Disqualifiers: Other malignancy, Active cerebral disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This clinical trial is studying lymphoma. Lymphoma is a cancer that starts in the blood cells that fight infection. There are several types of lymphoma. This study will enroll people who have classical Hodgkin lymphoma (cHL), peripheral T cell lymphoma (PTCL), or diffuse large B cell lymphoma (DLBCL). This clinical trial uses a drug called PF-08046044/SGN-35C . The study drug is in testing and has not been approved for sale. This is the first time SGN -35C will be used in people. This study will test the safety of SGN-35C in participants with lymphoma. It will also study the side effects of this drug. A side effect is anything a drug does to the body besides treating the disease. This study will have three parts. Parts A and B of the study will find out the best dose and dosing schedule for SGN-35C. Part C will use the dose found in parts A and B to find out how safe SGN-35C is and if it works to treat select lymphomas.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What is known about the safety of SGN-35C (Brentuximab Vedotin) in humans?

SGN-35C, also known as Brentuximab Vedotin, has been tested in clinical trials and is generally considered safe, with common side effects including nausea, fatigue, and fever. Serious side effects were rare but included infections like herpes zoster and pneumonia. The treatment has shown modest clinical activity in patients with certain types of lymphoma. ^{1 2 3 4 5}

How is the drug SGN-35C different from other lymphoma treatments?

SGN-35C, also known as brentuximab vedotin, is unique because it is an antibody-drug conjugate (ADC) that targets the CD30 antigen on lymphoma cells, delivering a potent cell-killing agent directly to the cancer cells. This targeted approach can enhance the drug's effectiveness while potentially reducing damage to healthy cells compared to traditional chemotherapy. ^{1 3 4 5 6}

Eligibility Criteria

This trial is for adults with certain types of lymphoma, including classical Hodgkin, peripheral T cell, and diffuse large B cell lymphomas. Participants must have tried several treatments already or be ineligible/refused them. They need a performance status score ≤1 and must provide tissue to check CD30 expression in their tumors.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

My cancer shows up on PET scans and can be measured with a CT scan.

My latest biopsy shows my tumor has CD30 expression of 1% or more.

Exclusion Criteria

I have had a stem cell transplant from a donor.

I haven't had another cancer or any remaining cancer signs in the last 3 years.

My cancer has spread to my brain or its coverings.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive SGN-35C to determine the best dose and dosing schedule

Approximately 1 year

Treatment Part B

Continuation of dose determination for SGN-35C

Approximately 1 year

Treatment Part C

Participants receive the determined dose of SGN-35C to evaluate safety and efficacy

Approximately 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

30-37 days after last study treatment

Treatment Details

Interventions

• SGN-35C (Monoclonal Antibodies)

Trial Overview SGN-35C is being tested for the first time in humans to treat various lymphomas. The study has three parts: determining the best dose and schedule (Parts A & B) and assessing safety/effectiveness at that dose (Part C).

Participant Groups

Group I: PF-08046044/SGN-35C Experimental Treatment 1 Intervention

PF-08046044/SGN-35C Monotherapy

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

City of Hope (City of Hope National Medical Center, City Of Hope Medical Center) Duarte, CA

IP Address: City of Hope Investigational Drug Services(IDS) Duarte, CA

UCSD Medical Center - Encinitas Encinitas, CA

UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion) La Jolla, CA

More Trial Locations

Who Is Running the Clinical Trial?

Seagen Inc. Lead Sponsor

Seagen, a wholly owned subsidiary of Pfizer Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma. [2020] Purpose This first-in-human study evaluated SGN-CD70A, an antibody-drug conjugate (ADC) directed against the integral plasma membrane protein CD70 and linked to a pyrrolobenzodiazepine (PBD) dimer, in patients with relapsed or refractory (R/R) CD70-positive non-Hodgkin lymphoma (NHL) including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Grade 3b follicular lymphoma (FL3b). Methods SGN-CD70A was administered intravenously on Day 1 of 3-week cycles beginning at 8 mcg/kg with planned dose escalation to 200 mcg/kg. Due to observations of prolonged thrombocytopenia, the study was amended to dose every 6 weeks (q6wk). Results Twenty patients were enrolled and treated with SGN-CD70A. The maximum tolerated dose of SGN-CD70A was 30 mcg/kg q6wk. The most common adverse events (AEs) reported were thrombocytopenia (75%), nausea (55%), anemia (50%), and fatigue (50%). The onset for treatment-related thrombocytopenia typically occurred during Cycle 1. Most of the treatment-related events of thrombocytopenia were ≥ Grade 3. Antitumor activity in patients included 1 complete remission (CR) and 3 partial remissions (PRs), 2 of which were ongoing for at least 42.9 weeks. SGN-CD70A exposures were approximately dose proportional, with a mean terminal half-life of 3 to 5 days. Conclusions While modest single-agent activity was observed in heavily pretreated NHL patients, the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term response with limited drug exposure.

2. United States pubmed.ncbi.nlm.nih.gov

A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. [2021] Phase 1 testing of SGN-30, a chimeric monoclonal antibody for the treatment of CD30(+) malignancies, was conducted in a multicenter study. To explore the safety profile and establish the maximum tolerated dose (MTD), 24 patients with refractory or relapsed Hodgkin lymphoma or CD30(+) non-Hodgkin lymphoma received 6 weekly doses of intravenous SGN-30 at 4 dose levels (2, 4, 8, or 12 mg/kg). Serum concentrations of SGN-30 rose rapidly and were dose dependent. Adverse events were mild, with nausea, fatigue, and fever attributed to study treatment. One episode of hypersensitivity rash was reported. The MTD was not reached. Serious adverse events included herpes zoster (n = 2), influenza, and pneumonia. One patient with cutaneous anaplastic large cell lymphoma (8 mg/kg) achieved a complete response. Six patients, of whom 4 had Hodgkin lymphoma, achieved stable disease with durations ranging from 6 to 16 months. The pharmacokinetic profile of SGN-30 showed a biphasic disposition, and estimated half-lives ranging between 1 to 3 weeks. The 6 weekly infusions of SGN-30 resulted in approximately 2- to 3-fold accumulation in serum exposures consistently across the dose range. These results demonstrate that weekly administration of SGN-30 is safe and has modest clinical activity in patients with CD30(+) tumors. This trial is registered at http://www.ClinicalTrials.gov as no. NCT00051597.

3. United States pubmed.ncbi.nlm.nih.gov

Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. [2021] SGN-35 is an antibody-drug conjugate (ADC) containing the potent antimitotic drug, monomethylauristatin E (MMAE), linked to the anti-CD30 monoclonal antibody, cAC10. As previously shown, SGN-35 treatment regresses and cures established Hodgkin lymphoma and anaplastic large cell lymphoma xenografts. Recently, the ADC has been shown to possess pronounced activity in clinical trials. Here, we investigate the molecular basis for the activities of SGN-35 by determining the extent of targeted intracellular drug release and retention, and bystander activities.

4. United States pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin (SGN-35). [2019] Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) directed against the CD30 antigen expressed on Hodgkin lymphoma and anaplastic large cell lymphoma. SGN-35 consists of the cAC10 chimerized IgG1 monoclonal antibody SGN30, modified by the addition of a valine-citrulline dipeptide linker to permit attachment of the potent inhibitor of microtubule polymerization monomethylauristatin E (MMAE). In phase II trials, SGN-35 produced response rates of 75% in patients with Hodgkin lymphoma (n = 102) and 87% in patients with anaplastic large cell lymphoma (n = 30). Responses to SGN-35 might be related not only to the cytotoxic effect due to release of MMAE within the malignant cell but also to other effects. First, SGN-35 may signal malignant cells through CD30 ligation to deliver an apoptotic or proliferative response. The former would amplify the cytotoxicity of MMAE. A proliferative signal delivered in the context of MMAE intoxication could enhance cell death. Second, the efficacy of SGN-35, particularly in Hodgkin lymphoma, might be attributed to its effect on the tumor microenvironment. Diffusion of free MMAE from the targeted tumor cells could result in a bystander effect that kills the normal supporting cells in close proximity to the malignant cells. The elimination of T regulatory cells that inhibit cytotoxic effector cells and elimination of cells that provide growth factor support for Hodgkin/Reed-Sternberg cells could further enhance the cytotoxic activity of SGN-35. Here we review the biology of SGN-35 and the clinical effects of SGN-35 administration.

5. England pubmed.ncbi.nlm.nih.gov

A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. [2022] SGN-30, a chimeric anti-CD30 monoclonal antibody, has demonstrated potent preclinical antitumour activity in both Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). We conducted an open-label, Phase II study to determine the safety and objective response rate of SGN-30 in 79 patients with refractory/recurrent HL (n = 38) or systemic ALCL (n = 41). Each course of SGN-30 comprised 6 weekly intravenous infusions, followed by a 2-week treatment-free period. Patients had received a median of 3 (range 1-5) prior regimens of chemotherapy or systemic therapy. The initial 40 patients received 6 mg/kg weekly; the latter 39 patients received 12 mg/kg weekly. In the ALCL group, two patients achieved a complete response and five additional patients achieved a partial response, with response durations ranging from 27 to 1460+ d. No objective responses were observed in the HL group; however, 11 patients (29%) had stable disease (duration 62-242 days). Although adverse events were common, most were mild or moderate, and no specific pattern of adverse events was observed in either disease group. These results demonstrate that weekly administration of SGN-30 is safe, with modest clinical activity in patients with ALCL.

6. England pubmed.ncbi.nlm.nih.gov

Phase I clinical study of brentuximab vedotin (SGN-35) involving children with recurrent or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large cell lymphoma: rationale, design and methods of BV-HLALCL study: study protocol. [2019] Hodgkin's lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) are the two most common tumors expressing CD30. Internationally, a clinical study that is being conducted involving adults with recurrent or refractory HL or ALCL suggests efficacy of brentuximab vedotin (SGN-35). Pediatric patients should be given medicines that have been appropriately evaluated for their use. In the past, however, new approved drugs have been used for pediatric patients without the confirmation of safety and efficacy in pediatric patients. Therefore, it is important to examine the safety and efficacy of SGN-35 in Japanese children.