Safety Study of SEA-CD40 in Cancer Patients

Lymphoma Clinical Trial

Official title:

A Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02376699
• Other study ID #: SGNS40-001
• Secondary ID: PN 863
• Status: Terminated
• Phase: Phase 1
• Start date: February 28, 2015
• Est. completion date: April 14, 2023

Study information

• Verified date: April 2023
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study will be conducted in the following parts:

Part A: Intravenous (IV) monotherapy dose-regimen finding for solid tumors -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the IV SEA-CD40 monotherapy maximum tolerated dose (MTD) and/or the optimal biological dose (OBD) regimens in patients with solid tumors. The ability to increase the dose intensity (to give additional doses within a treatment cycle) may be evaluated.

Part B: IV monotherapy solid tumor expansion cohorts -- Disease-specific solid tumor expansion cohorts may be enrolled where patients will be treated with doses at or below the IV SEA-CD40 monotherapy MTD and/or OBD determined in Part A.

Part C: IV monotherapy dose-regimen finding for lymphomas -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the IV SEA-CD40 monotherapy MTD and/or the OBD regimens in patients with lymphomas. The ability to increase the dose intensity (to give additional doses within a treatment cycle) may be evaluated.

Part D: IV monotherapy lymphoma expansion cohorts -- Disease-specific lymphoma expansion cohorts may be enrolled where patients will be treated with doses at or below the IV SEA-CD40 monotherapy MTD and/or OBD determined in Part C.

Part E: Combination therapy dose-regimen finding for solid tumors -- IV SEA-CD40 dose-escalation to define the MTD and/or the OBD regimen to be administered in combination with standard approved dose of pembrolizumab in patients with solid tumors.

Part F: Combination therapy solid tumor expansion cohorts -- Disease-specific solid tumor expansion cohorts may be enrolled where patients will be treated with IV SEA-CD40 and pembrolizumab combination therapy; doses of SEA-CD40 will be at or below the MTD and/or OBD determined in Part E.

Part G: Subcutaneous (SC) injection (injected under the skin) monotherapy dose-regimen finding for solid tumors -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the SC SEA-CD40 monotherapy maximum tolerated dose (MTD) and/or the optimal biological dose (OBD) regimens in patients with solid tumors.

Part H: SC monotherapy solid tumor expansion cohorts -- Disease-specific solid tumor expansion cohorts may be enrolled where patients will be treated with doses at or below the SC SEA-CD40 monotherapy MTD and/or OBD determined in Part G.

(Note: There is no Part I)

Part J: SC monotherapy dose-regimen finding for lymphomas -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the SC SEA-CD40 monotherapy MTD and/or the OBD regimens in patients with lymphomas.

Part K: SC monotherapy lymphoma expansion cohorts -- Disease-specific lymphoma expansion cohorts may be enrolled where patients will be treated with doses at or below the SC SEA-CD40 monotherapy MTD and/or OBD determined in Part J.

Part L: Combination therapy in pancreatic cancer -- Patients will be treated with SEA-CD40 doses at or below MTD and/or OBD. An established dose of pembrolizumab and a standard regimen of gemcitabine and nab-paclitaxel will be used.

In Parts A, C, E, G, and J, a maximum feasible dose (MFD) will be defined if an MTD and/or OBD cannot be identified. Parts B, D, F, H, K. and L will explore the recommended dosing regimen once the MTD and/or OBD, or MFD (if the MTD and/or OBD cannot be identified) has been determined.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 159
• Est. completion date: April 14, 2023
• Est. primary completion date: March 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Hodgkin Disease
• Lung Neoplasms
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Melanoma
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Head and Neck
• Neoplasms, Squamous Cell
• Non-small Cell Carcinoma
• Non-Small Cell Lung Cancer
• Non-Small Cell Lung Cancer Metastatic
• Pancreatic Adenocarcinoma
• Squamous Cell Cancer
• Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Squamous Cell Neoplasm

Intervention

Drug:
• Intravenous (IV) SEA-CD40
Given intravenously; schedule is cohort-specific.
• Pembrolizumab
Given intravenously; schedule is cohort-specific.
• Subcutaneous (SC) SEA-CD40
Given subcutaneously on Day 1 every 3 weeks
• Gemcitabine
1000 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle
• Nab-paclitaxel
125 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	UNC Lineberger Comprehensive Cancer Center / University of North Carolina	Chapel Hill	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Case Western Reserve University / University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	Providence Portland Medical Center	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Angeles Clinic and Research Institute, The	Santa Monica	California
United States	HonorHealth Scottsdale Shea Medical Center	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (Parts A-K)		Through 6 weeks following last dose, up to an average of 6 months
Primary	Incidence of laboratory abnormalities (Parts A-K)		Through 6 weeks following last dose, up to an average of 6 months
Primary	Objective response rate (ORR) per RECIST according to investigator assessment in the efficacy-evaluable population (Part L)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	Incidence of adverse events (Part L)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	ORR per iRECIST (Part L)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	ORR (Parts A-K)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	Disease control rate (All Parts)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	Duration of response (All Parts)		Up to approximately 6 years
Secondary	Progression-free survival (All Parts)		Up to approximately 6 years
Secondary	Overall survival (All Parts)		Up to approximately 6 years
Secondary	Cmax (maximum observed concentration)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	Tmax (time of maximum observed concentration)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	AUClast (AUC from time 0 to last quantifiable timepoint)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	AUCinf (AUC from time 0 to infinity)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	Apparent total clearance		Through 6 weeks following last dose, up to an average of 6 months
Secondary	T1/2 (apparent terminal elimination half-life)		Through 6 weeks following last dose, up to an average of 6 months
Secondary	Incidence of antitherapeutic antibodies against SEA-CD40		Through 6 weeks following last dose, up to an average of 6 months
Secondary	Blood concentrations of SEA-CD40		Through 6 weeks following last dose, up to an average of 6 months