Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Infections

Uterine Cervical Neoplasms

Recurrence

Carcinoma

Papilloma

Virus Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Vaccines

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

PRGN-2009 at a dose of 5 x 10\^11 PU q3W for 3 administrations, then q6w, plus Pembrolizumab, 400mg q6w

Subjects randomized will receive PRGN-2009 (5 x 10\^11 PU, subcutaneous (SC) injection) every 3 weeks for three administrations, thereafter subjects will continue to receive PRGN-2009 administrations every 6 weeks. Pembrolizumab will be administered concurrently as intravenous (IV) infusion (400 mg) every 6 weeks.

PRGN-2009 plus Pembrolizumab

Subjects randomized will receive IV infusion of pembrolizumab (400 mg) administered every 6 weeks.

Pembrolizumab alone

Amy Lankford

Matthew Kovak

Erica Redmond

John Liao, MD

This randomized trial will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab compared to pembrolizumab alone in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer.

This is a randomized, two-arm study of PRGN-2009 in patients with recurrent or metastatic cervical cancer who are pembrolizumab resistant. Patients meeting all eligibility criteria who consent to participate in the study will be randomized 1:1 to receive a combination of PRGN-2009, plus pembrolizumab, or to receive pembrolizumab alone.

PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer

A Randomized, Open-label, Two-arm, Phase 2 Study to Evaluate Efficacy and Safety of PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer.

The ORR will be calculated as the combination of subjects achieving a complete response or a partial response per RECIST v1.1.

ORR will be calculated and presented with 2-sided 95% confidence interval.

Systemic toxicity will be assessed through the capture of Treatment Emergent Adverse Events ( TEAEs). The severity of the TEAEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale.

Duration of PFS and OS will be summarized using the Kaplan-Meier Product Limit estimator along with the corresponding two sided-95% Confidence intervals.

The proportion of subjects with BOR and DCR will be summarized using descriptive statistics.

TTR and DOR will be summarized using descriptive statistics.

Samples collected before and at specific intervals after treatment will be evaluated for presence of adenoviral vector.

National Cancer Institute (NCI)

Precigen, Inc

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antibodies

Immunoglobulins

Encorafenib, binimetinib and pembrolizumab. Doses as determined in phase I

Pembrolizumab with a dose of 200 mg every 3 weeks.

Dose determined in phase I. Start dose: 450 mg qd

Encorafenib

Dose determined in phase I. Start dose: 45 mg bid

Binimetinib

Dose determined in phase I. Start dose: 200 mg q3w

Dirk Schadendorf, Prof. Dr.

This study will investigate the influence of maintenance therapy on progression-free survival (PFS) and overall survival (OS) after combination therapy with BRAF/MEK (MAP-ERK kinase) inhibitors and PD-1 antibody pembrolizumab.

In the safety phase I part the optimal dose of pembrolizumab in combination with BRAF inhibitor and MEK inhibitor and the safety of this three-drugs-combination regime will be determined.

In the randomized part 2 different maintenance therapies will be tested for toxicity and efficacy. Patients with disease control after 6 months of triple therapy will be randomized to receive 2 different maintenance therapies further on, either continuation of triple therapy or administration of pembrolizumab alone.

There is growing interest to understand the best strategies to use targeted therapies and novel immunotherapy for the treatment of advanced melanoma. This study will explore the combination of encorafenib plus binimetinib with the PD-1 antibody pembrolizumab in patients with BRAF mutant melanoma. Combination of two clinically effective approaches, targeting the mutant BRAF pathway by BRAF/MEK inhibition and modulating immunological checkpoint control by administration of a PD-1 antibody, should prolong PFS and OS even further. This study will investigate the influence of maintenance therapy on PFS and OS after triple therapy. Patients with disease control after 6 months of triple therapy will be randomized to receive 2 different maintenance therapies further on to investigate if administration of pembrolizumab only is sufficient for maintenance of disease control. For reasons of safety a phase I study is performed to determine the optimal dosing and schedule of the combination therapy (encorafenib, binimetinib, pembrolizumab).

In the phase II-part, patient will receive triple therapy with the doses defined in phase I for a 6 months induction period. Patients with complete or partial response or stable disease after the 6 months period will be randomized for maintenance therapy:

Arm A: Therapy as in induction period. Arm B: Therapy with pembrolizumab only with a dose of 200 mg every 3 weeks.

Encorafenib + Binimetinib + Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

A Randomized Phase I / II Open Label, Multicentre Study of Encorafenib Plus Binimetinib and PD-1 Antibody Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

Dose limiting toxicities (DLT) will be determined within 42 days of therapy start (first pembrolizumab injection) and are defined as all ≥ grade 4 hematological toxicities and certain non-hematological toxicities ≥ CTCAE grade 3.

Time from administration of first study drug to the date of first documented progression (according Recist criteria version 1.1) or death due to any cause, whichever occurs first.

Rate of patients with PFS after 12 months of therapy

Rate of patients with PFS after 18 months of therapy

Number of patients with PFS after 24 months of therapy

All adverse events (AEs) / serious adverse events (SAEs) NCI CTCEA (Common Terminology Criteria for Adverse Events) Grade ≥ 3

Number of patients with complete response (CR), partial response (PR) and stable disease (SD) as best response.

Time from the date of first administration of study drug to the date of death due to any cause.

Number of patients alive in the time period from date of first administration of study drug until 1 year after date of first administration

Number of patients alive in the time period from date of first administration of study drug until 2 years after date of first administration

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer	NCT06157151	Cervical Cancer HPV-Related Car... HPV-Related Mal...	PRGN-2009 plus ... Pembrolizumab a...	18 Years -	Precigen, Inc
PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer	NCT06157151	Cervical Cancer HPV-Related Car... HPV-Related Mal...	PRGN-2009 plus ... Pembrolizumab a...	18 Years -	Precigen, Inc
Encorafenib + Binimetinib + Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma	NCT02902042	Malignant Melan...	Encorafenib Binimetinib Pembrolizumab Pembrolizumab a...	18 Years -	University Hospital, Essen
Encorafenib + Binimetinib + Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma	NCT02902042	Malignant Melan...	Encorafenib Binimetinib Pembrolizumab Pembrolizumab a...	18 Years -	University Hospital, Essen

Spots Global Cancer Trial Database for pembrolizumab alone