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Pembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 for the Treatment of Patients With Recurrent Ovarian Cancer

ConditionsOvarian Clear Cell AdenocarcinomaPlatinum-Sensitive Ovarian CarcinomaRecurrent Endometrial Serous AdenocarcinomaRecurrent Fallopian Tube CarcinomaRecurrent Fallopian Tube Endometrioid AdenocarcinomaRecurrent Fallopian Tube Serous AdenocarcinomaRecurrent Ovarian CarcinomaRecurrent Ovarian Clear Cell AdenocarcinomaRecurrent Ovarian Endometrioid AdenocarcinomaRecurrent Ovarian Serous AdenocarcinomaRecurrent Platinum-Resistant Ovarian CarcinomaRecurrent Primary Peritoneal CarcinomaRecurrent Primary Peritoneal Clear Cell AdenocarcinomaRecurrent Primary Peritoneal Endometrioid AdenocarcinomaRecurrent Primary Peritoneal Serous Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorRoswell Park Cancer Institute

About this trial

This phase II trial tests whether pembrolizumab combined with bevacizumab with or without agonist anti-CD40 CDX-1140 works to shrink tumors in patients with ovarian cancer that has come back (recurrent). Anti-CD40 CDX-1140 works by stimulating certain immune cells within the tumor and, when combined with other immunotherapy treatments, may increase antitumor antibody production. Immunotherapy with monoclonal antibodies, such as pembrolizumab and bevacizumab, may help the body's immune system, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and bevacizumab with anti-CD40 CDX-1140 may decrease symptoms, prolong survival, and improve quality of life in patients with ovarian cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age >= 18 years of age.

Recurrent serous (low grade or high grade), endometrioid, or clear cell recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Participant can be either platinum-sensitive or platinum-resistant, no more than 4 prior lines of treatment, and BRCA status must be known.

Participants may have received a prior PARPi, this will not be considered a separate line of therapy if received in maintenance.

Disqualifiers

Primary platinum-refractory patients are excluded

Has a nonepithelial cancer (germ cell tumors, sex cord-stromal tumors), borderline tumors, mucinous or seromucinous that is predominately mucinous, malignant Brenner's tumor, carcinosarcoma or undifferentiated carcinoma.

Receipt of any antibody targeting T cell checkpoint or co-stimulation pathways within 4 weeks, use of any other monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks prior to the planned start of study treatment.

Has received prior systemic anticancer therapy (including investigational agents or maintenance therapy) within 28 days prior to the planned start of study treatment.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Anti-CD40 Agonist Monoclonal Antibody CDX-1140

    Biological/Vaccine

    Given IV

  • Bevacizumab

    Biological/Vaccine

    Given IV

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Quality-of-Life Assessment

    Other intervention

    Ancillary studies

  • Questionnaire Administration

    Other intervention

    Ancillary studies

Treatment groups

80 Participants
are divided into 2 treatment groups
Group A: Arm I (pembrolizumab, bevacizumab)Active comparator 4 interventions
Group B: Arm II (pembrolizumab, bevacizumab, CDX-1140)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Incidence of adverse events

Evaluated according to National Cancer Institute Common Terminology Criteria for adverse events (NCI CTCAE) version (v)5.0. Will be summarized by cohort and grade using frequencies and relative frequencies.

Time frame
Up to 2 years
2

Objective response rate (ORR)

Will be summarized by cohort (with or without CDX 1140) using frequencies and relative frequencies, with the ORR estimated using 90% confidence intervals obtained by Jeffrey's prior method. The final analysis will be performed on all n=80 (40 in each cohort) evaluable patients; and if the p-value is less than or equal to 0.10, then the triplet regimen will be considered superior with respect to response.

Time frame
From first day of treatment Up to 6 months.

Secondary outcomes

1

Progression free survival (PFS)

Will be summarized by cohort using standard Kaplan-Meier methods, with estimates of the median obtained with 90% confidence intervals. PFS will be compared between cohorts using a one-sided log-rank test.

Time frame
From first day of treatment until disease progression or date of death from any cause, assessed up to 2 years
2

Overall survival (OS)

Will be summarized by cohort using standard Kaplan-Meier methods, with estimates of the median obtained with 90% confidence intervals. OS will be compared between cohorts using a one-sided log-rank test.

Time frame
From first day of treatment until disease progression or date of death from any cause, assessed up to 2 years
3

Disease control rate (DCR)

Will be summarized by cohort using frequencies and relative frequencies, with the DCR estimated by cohort using 90% confidence intervals obtained by Jeffrey's prior method. The DCR will be compared between cohorts using a one-sided Cohran-Mantel-Haenszel test.

Time frame
Up to 2 years
4

Quality of Life (QoL)EORTC QLQ-C30

European Organization for Research and Treatment of Cancer (EORTC) QLQ-30 consists of 28 questions with answers that range from 1 (Not At All) to 4 (Very Much) and 2 questions that range from 1 (Very Poor) to 7 (Excellent)

Time frame
Up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Roswell Park Cancer Institute

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

Celldex Therapeutics

Collaborator

United States Department of Defense

Collaborator

Source ClinicalTrials.gov
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