Safety Study of SEA-CD40 in Cancer Patients

Sponsor

Seagen Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02376699

Collaborator

Merck Sharp & Dohme LLC (Industry)

159

Enrollment

Locations

Arms

116.1

Anticipated Duration (Months)

8.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Hodgkin Disease Lymphoma Lymphoma, B-Cell Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Melanoma Neoplasm Metastasis Neoplasms, Head and Neck Neoplasms, Squamous Cell Non-Small Cell Lung Cancer Non-Small Cell Lung Cancer Metastatic Non-small Cell Carcinoma Squamous Cell Cancer Squamous Cell Carcinoma Squamous Cell Carcinoma of the Head and Neck Squamous Cell Neoplasm Lymphoma, Non-Hodgkin Pancreatic Adenocarcinoma	Drug: Intravenous (IV) SEA-CD40 Drug: Pembrolizumab Drug: Subcutaneous (SC) SEA-CD40 Drug: Gemcitabine Drug: Nab-paclitaxel	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

159 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 28, 2015

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Oct 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IV Monotherapy in Solid Tumors SEA-CD40 administered IV	Drug: Intravenous (IV) SEA-CD40 Given intravenously; schedule is cohort-specific. Other Names: SEA-CD40
Experimental: IV Monotherapy in Lymphomas SEA-CD40 administered IV	Drug: Intravenous (IV) SEA-CD40 Given intravenously; schedule is cohort-specific. Other Names: SEA-CD40
Experimental: Combination Therapy in Solid Tumors SEA-CD40 (administered IV) + pembrolizumab	Drug: Intravenous (IV) SEA-CD40 Given intravenously; schedule is cohort-specific. Other Names: SEA-CD40 Drug: Pembrolizumab Given intravenously; schedule is cohort-specific. Other Names: Keytruda
Experimental: SC Monotherapy in Solid Tumors SEA-CD40 administered SC	Drug: Subcutaneous (SC) SEA-CD40 Given subcutaneously on Day 1 every 3 weeks Other Names: SEA-CD40
Experimental: SC Monotherapy in Lymphomas SEA-CD40 administered SC	Drug: Subcutaneous (SC) SEA-CD40 Given subcutaneously on Day 1 every 3 weeks Other Names: SEA-CD40
Experimental: Combination Therapy in Pancreatic Cancer SEA-CD40 (administered IV) + pembrolizumab + gemcitabine + nab-paclitaxel	Drug: Intravenous (IV) SEA-CD40 Given intravenously; schedule is cohort-specific. Other Names: SEA-CD40 Drug: Pembrolizumab Given intravenously; schedule is cohort-specific. Other Names: Keytruda Drug: Gemcitabine 1000 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle Other Names: Gemzar Drug: Nab-paclitaxel 125 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle Other Names: Abraxane

Outcome Measures

Primary Outcome Measures

Incidence of adverse events (Parts A-K) [Through 6 weeks following last dose, up to an average of 6 months]
Incidence of laboratory abnormalities (Parts A-K) [Through 6 weeks following last dose, up to an average of 6 months]
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 Outcome Measures

Incidence of adverse events (Part L) [Through 6 weeks following last dose, up to an average of 6 months]
ORR per iRECIST (Part L) [Through 6 weeks following last dose, up to an average of 6 months]
ORR (Parts A-K) [Through 6 weeks following last dose, up to an average of 6 months]
Disease control rate (All Parts) [Through 6 weeks following last dose, up to an average of 6 months]
Duration of response (All Parts) [Up to approximately 6 years]
Progression-free survival (All Parts) [Up to approximately 6 years]
Overall survival (All Parts) [Up to approximately 6 years]
Cmax (maximum observed concentration) [Through 6 weeks following last dose, up to an average of 6 months]
Tmax (time of maximum observed concentration) [Through 6 weeks following last dose, up to an average of 6 months]
AUClast (AUC from time 0 to last quantifiable timepoint) [Through 6 weeks following last dose, up to an average of 6 months]
AUCinf (AUC from time 0 to infinity) [Through 6 weeks following last dose, up to an average of 6 months]
Apparent total clearance [Through 6 weeks following last dose, up to an average of 6 months]
T1/2 (apparent terminal elimination half-life) [Through 6 weeks following last dose, up to an average of 6 months]
Incidence of antitherapeutic antibodies against SEA-CD40 [Through 6 weeks following last dose, up to an average of 6 months]
Blood concentrations of SEA-CD40 [Through 6 weeks following last dose, up to an average of 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Prior chemotherapy, small molecule inhibitors, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies) within 4 weeks
Prior radiotherapy: therapeutic radiotherapy within 4 weeks, or palliative radiotherapy (to non-CNS disease) within 1 week
Prior immune-checkpoint inhibitors within 4 weeks (or 8 weeks, if immuno-oncology doublet used as the prior line of therapy)
Prior monoclonal antibodies, antibody-drug conjugates, or radioimmunoconjugates within 4 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
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

History of radiation pneumonitis
Neuropathy Grade 2 or higher
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
Has had allogenic tissue/solid organ transplant

All Parts

Recent or ongoing serious infections within 2 weeks
Known positivity for hepatitis B infection
Known active hepatitis C infection
Active autoimmune or auto-inflammatory ocular disease within 6 months
Known or suspected active organ-threatening autoimmune disease
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
2	HonorHealth Scottsdale Shea Medical Center	Scottsdale	Arizona	United States	85258
3	Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California	United States	90048
4	Angeles Clinic and Research Institute, The	Santa Monica	California	United States	90404
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	University of Chicago Medical Center	Chicago	Illinois	United States	60637-1470
7	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
8	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan	United States	48201
9	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
10	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
11	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
12	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131
13	Montefiore Medical Center	Bronx	New York	United States	10467
14	UNC Lineberger Comprehensive Cancer Center / University of North Carolina	Chapel Hill	North Carolina	United States	27599
15	Case Western Reserve University / University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
16	Providence Portland Medical Center	Portland	Oregon	United States	97213
17	MD Anderson Cancer Center / University of Texas	Houston	Texas	United States	77030-4095
18	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
19	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington	United States	98109-1023