Safety Study of SEA-CD40 in Cancer Patients

• Status: Active, not recruiting
• Trial end date: 2024-02-29
• Target enrollment: 0
• Participant gender: All

Summary

This study is being done to find out if SEA-CD40 is safe and effective when given alone, in combination with pembrolizumab, and in combination with pembrolizumab, gemcitabine, and nab-paclitaxel. The study will test increasing doses of SEA-CD40 given at least every 3 weeks to small groups of patients. The goal is to find the highest dose of SEA-CD40 that can be given to patients that does not cause unacceptable side effects. Different dose regimens will be evaluated. Different methods of administration may be evaluated. The pharmacokinetics, pharmacodynamic effects, biomarkers of response, and antitumor activity of SEA-CD40 will also be evaluated.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Seagen Inc.; Seattle Genetics, Inc.
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Gemcitabine; Paclitaxel; Pembrolizumab

Criteria

Inclusion Criteria:

• (Monotherapy - Parts A, B, C, D, G, H, J, and K) -- Histologically confirmed advanced malignancy, either: (a) Metastatic or unresectable solid malignancy; or (b) Classical Hodgkin lymphoma (HL), or diffuse large B-cell lymphoma (DLBCL), or indolent lymphoma (including follicular lymphoma [FL])

• (Monotherapy - Parts A, B, C, D, G, H, J, and K) -- Relapsed, refractory, or progressive disease, specifically: (a) Solid tumors: Following at least 1 prior systemic therapy, and no further standard therapy is available for the patient's advanced solid tumor at the time of enrollment; or (b) Classical HL: Following at least 2 prior systemic therapies in patients who are not candidates for autologous stem cell transplant (SCT), or following failure of autologous SCT; or (c) DLBCL: Following at least 1 prior systemic therapy; patients must have also received intensive salvage therapy unless they refused or were deemed ineligible; or (d) Indolent lymphoma: Following at least 1 prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists

• (Combination Therapy - Part E and Part F) -- Histologically or cytologically confirmed advanced or metastatic solid malignancy for which pembrolizumab treatment is approved. In Part F, other advanced solid tumor indications may be eligible as identified by the Sponsor.

• (Pancreatic Cancer Cohort - Part L) - Histologically or cytologically confirmed metastatic exocrine ductal adenocarcinoma of the pancreas not amenable to curative therapy. Patients must not have received any prior systemic therapy for metastatic disease; patients who have received prior therapy for non-metastatic pancreatic adenocarcinoma are eligible if therapy was fully completed more than 4 months before start of study treatment.

• Representative baseline tumor tissue sample is available (Parts A-K)

• Measurable disease

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Adequate baseline hematologic, renal, and hepatic function

• Recovery to Grade 1 of any clinically significant toxicity attributed to prior anticancer therapy prior to initiation of study drug administration

Exclusion Criteria:

• Parts A-K

1. Prior chemotherapy, small molecule inhibitors, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies) within 4 weeks

2. Prior radiotherapy: therapeutic radiotherapy within 4 weeks, or palliative radiotherapy (to non-CNS disease) within 1 week

3. Prior immune-checkpoint inhibitors within 4 weeks (or 8 weeks, if immuno-oncology doublet used as the prior line of therapy)

4. Prior monoclonal antibodies, antibody-drug conjugates, or radioimmunoconjugates within 4 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)

5. Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)

• Part L

1. History of radiation pneumonitis

2. Neuropathy Grade 2 or higher

3. Has received prior therapy with an anti-PD-1, anti-PDL1, or anti-PD-L2 agent, with an agent directed to another stimulatory or co-inhibitory T-cell receptor

4. Has had allogenic tissue/solid organ transplant

• All Parts

1. Recent or ongoing serious infections within 2 weeks

2. Known positivity for hepatitis B infection

3. Known active hepatitis C infection

4. Active autoimmune or auto-inflammatory ocular disease within 6 months

5. Known or suspected active organ-threatening autoimmune disease

6. Active central nervous system tumor or metastases

• Patients with lymphomas: prior allogeneic SCT

• Patients in Part E, F, or L: history of severe immune-mediated adverse reactions or severe hypersensitivity to pembrolizumab