A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies

• ClinicalTrials.gov Identifier: NCT03329950
• Recruitment Status: Completed
• First Posted: November 6, 2017
• Last Update Posted: September 29, 2022
• Sponsor: Celldex Therapeutics
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Celldex Therapeutics

Tracking Information

• First Submitted Date: October 23, 2017
• First Posted Date: November 6, 2017
• Last Update Posted Date: September 29, 2022
• Actual Study Start Date: December 1, 2017
• Actual Primary Completion Date: September 13, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2020)

Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0 [ Time Frame: From first dose through 30 days after last dose ]

The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.

Original Primary Outcome Measures (submitted: October 31, 2017)

Safety and Tolerability of CDX1140-01 as assessed by CTCAE v4.0 [ Time Frame: Within 28 days after first dose ]

The rates of drug-related adverse events, serious drug-related adverse events, dose-limiting toxicities, laboratory test abnormalities, and maximum tolerated dose will be determined.

Current Secondary Outcome Measures (submitted: August 12, 2020)

• Objective Response Rate [ Time Frame: Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years. ]
  The percentage of patients who achieved a confirmed complete response or partial response by evaluation criteria in solid tumors for immune-based therapeutics (iRECIST; for solid tumor patients) and the lymphoma response to immunomodulatory therapy criteria (LYRIC; for lymphoma patients).
• Clinical benefit rate [ Time Frame: Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years ]
  The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months
• Duration of Response [ Time Frame: First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years) ]
  The interval from which measurement criteria are first met for CR or PR until the first date that progressive disease is objectively documented
• Progression-free survival [ Time Frame: From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years) ]
  The time from start of study drug to time of progression or death, whichever occurs first
• Overall survival [ Time Frame: The time from start of study drug to death from any cause (up to approximately 1-3 years) ]
  The time from start of study drug to death
• Immunogenicity evaluation [ Time Frame: Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years ]
  Serum samples will be obtained for assessment of human anti-CDX-1140 and anti-CDX-301 antibodies
• Pharmacokinetic evaluation [ Time Frame: Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years ]
  CDX-1140 and CDX-301 concentrations will be measured

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies
• Official Title: A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies
• Brief Summary: This is a study to determine the maximum tolerated dose (MTD) for CDX-1140 (CD40 antibody), either alone or in combination with CDX-301 (FLT3L), pembrolizumab, or chemotherapy and to further evaluate its tolerability and efficacy in expansion cohorts once the MTD is determined.

Detailed Description

This study will determine the MTD of CDX-1140 while also evaluating the safety, tolerability and efficacy of CDX-1140 alone (Part 1) or in combination with CDX-301 (Part 2), pembrolizumab (Part 3), or chemotherapy (Part 4) in patients with cancer.

Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-1140. The dose-escalation part of the study will test the safety profile of CDX-1140, alone or in combination with CDX-301, pembrolizumab or chemotherapy and determine which dose(s) of CDX-1140 will be studied in the expansion portions of the study.

All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Melanoma
• Non-small Cell Lung Cancer
• Breast Cancer
• Gastric Cancer
• Renal Cell Carcinoma
• Ovarian Cancer
• Cholangiocarcinoma
• Bladder Urothelial Carcinoma
• Pancreatic Adenocarcinoma
• Colorectal Cancer
• Esophageal Cancer
• Hepatic Cancer
• Head and Neck Cancer
• Primary Peritoneal Cancer
• Fallopian Tube Cancer
• Other Solid Tumors
• Diffuse Large B-cell Lymphoma (DLBCL)
• Mantle Cell Lymphoma
• Indolent B-cell Lymphomas
• Non-Hodgkin Lymphoma
• Follicular Lymphoma
• Lymphoplasmacytic Lymphoma
• Waldenstrom's Disease
• Marginal Zone Lymphoma
• Mucosa Associated Lymphoid Tissue
• Small Lymphocytic Leukemia

Intervention

• Drug: CDX-1140
  CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.
• Drug: CDX-301
  CDX-301 will be injected once a day for five days before Cycles 1 and 2.
• Drug: Pembrolizumab
  Pembrolizumab will be administered every 3 weeks.
• Drug: Chemotherapy
  Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.

Study Arms

• Experimental: CDX-1140
  Part 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment.
  Intervention: Drug: CDX-1140
• Experimental: CDX-1140 and CDX-301
  Part 2: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance or two years of treatment. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.
  Interventions:

  • Drug: CDX-1140
  • Drug: CDX-301
• Experimental: CDX-1140 and pembrolizumab
  Part 3: Eligible patients will receive CDX-1140, based on cohort assigned, in 3 week cycles until progression, or intolerance, or two years of treatment. A fixed dose of pembrolizumab will also be given in 3 week cycles.
  Interventions:

  • Drug: CDX-1140
  • Drug: Pembrolizumab
• Experimental: CDX-1140 and chemotherapy
  Part 4: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, or intolerance, or two years of treatment. Chemotherapy will also be given according to standard of care.
  Interventions:

  • Drug: CDX-1140
  • Drug: Chemotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 25, 2022): 132
• Original Estimated Enrollment (submitted: October 31, 2017): 105
• Actual Study Completion Date: September 13, 2022
• Actual Primary Completion Date: September 13, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Recurrent, locally advanced or metastatic melanoma (including mucosal and/or ocular), bladder/urothelial, non-small cell lung cancer, pancreatic adenocarcinoma, breast, colorectal, gastric, esophageal, renal cell, hepatic, ovarian fallopian or primary peritoneal carcinoma, head and neck, and cholangiocarcinoma. Additional tumor types (except primary CNS tumors) may be enrolled after discussion with, and approval from, the medical monitor.
2. Must have received all standard of care therapies (approved or unapproved) as deemed appropriate by the treating physician. Patients who refuse standard therapy are excluded from the study.
3. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 3 months following last treatment
4. Willingness to undergo a pre-treatment and on-treatment biopsy, if required.

Additional Inclusion Criteria for Part 1:

1. Advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or indolent B-cell lymphoma are also eligible.
2. Lymphoma patients must have received ≥ 1 prior systemic therapy

Additional Inclusion Criteria for Part 3:

1. Patients must have documented progression while receiving anti-PD-1 or anti-PD-L1 based regimens for FDA approved indications
2. Patients cannot have received more than one anti-PD-1 or anti-PD-L1 based regimen

Additional Inclusion Criteria for Part 4:

1. Patients must have metastatic pancreatic adenocarcinoma, and have not received previous treatment in a metastatic setting

Key Exclusion Criteria:

1. History of severe hypersensitivity reactions to other monoclonal antibodies.
2. Previous treatment with any anti-CD40 antibody or with FLT3L.
3. Inadequate washout period from prior therapy as defined in the Protocol.
4. Major surgery within 4 weeks prior to study treatment.
5. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to study treatment.
6. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers. For all other cancers, the patient must be disease-free for at least 3 years to be allowed to enroll.
7. Active, untreated central nervous system metastases.
8. Active autoimmune disease or documented history of autoimmune disease.
9. History of (non-infectious) pneumonitis or has current pneumonitis.
10. Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or Hepatitis C.

Additional Exclusion Criteria for lymphoma patients in Part 1:

1. Prior allogenic stem cell transplantation
2. Patients who have received autologous stem cell transplant ≤ 12 weeks prior to the first dose of study drug.

There are additional criteria your study doctor will review with you to confirm your eligibility for the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03329950
• Other Study ID Numbers: CDX1140-01; Keynote-A23 ( Other Identifier: Merck )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Celldex Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Celldex Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: Celldex Therapeutics
• Verification Date: April 2022