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Immunologic Factors

Sodium Cridanimod and progestin therapy (megestrol acetate) combination

The study will investigate the efficacy of Sodium Cridanimod in conjunction with progestin therapy in a population of subjects with endometrial cancer, who have failed progestin monotherapy or who have been identified as PrR negative.

Sodium Cridanimod

The study will investigator the use of progestin therapy in conjunction with Sodium Cridanimod

progestin therapy

Curtis Lockshin, PhD

This is an open-label, multi-center, single-arm, two-period Phase 2 study. The study will investigate the efficacy of Sodium Cridanimod in conjunction with progestin therapy in a population of subjects with recurrent or persistent endometrial cancer, who have failed progestin monotherapy or who have been identified as Progesterone Receptor (PrR) negative. All patients must have endometrial cancer PrR status determined from an archival sample at Screening. The PrR status (positive or negative) will be determined by central laboratory by ImmunoHistoChemistry (IHC) testing.

There are two treatment periods and a follow-up period within the study.

Treatment Period 1 (Progestin Monotherapy): During Treatment Period 1, all subjects determined to be PrR positive will receive progestin monotherapy, megestrol acetate, for up to 24 weeks. Subjects will have an MRI or CT scan after 12 and 24 weeks of progestin monotherapy, with response to treatment being assessed according to RECIST 1.1 criteria. All subjects that achieve disease control confirmed by tumor assessment after Treatment Period 1, will be ineligible to enter Treatment Period 2. These subjects will be terminated from the trial and treated according to local standards of practice, which may include continued progestin therapy.

Subjects determined to be PrR negative at Screening will not enroll into Treatment Period 1. These subjects will enroll directly into Treatment Period 2.

Treatment Period 2 (Combination Treatment): All subjects determined to be PrR negative at Screening and those who received at least 4 weeks of progestin monotherapy and who experienced disease progression at the conclusion of Treatment Period 1 will enter Treatment Period 2 of the study. During Treatment Period 2, subjects will receive Sodium Cridanimod in combination with continued progestin treatment, megestrol acetate. Subjects will receive treatment until disease progression as defined according to RECIST 1.1 criteria, with response assessments performed at 12-week intervals.

Follow-up Period: Once subjects progress during Treatment Period 2, they will return for a Safety Follow-up Visit 4 weeks following the last treatment, and then continue to be followed for an additional 12-month period for overall survival.

An Endometrial Cancer Study for Women With Recurrent or Persistent Endometrial Cancer

A Phase 2, Single Arm, Two Period Study of Sodium Cridanimod in Conjunction With Progestin Therapy in Patients With Endometrial Carcinoma

Subjects in the Full Analysis Set (FAS) population will be assessed for ODC. The FAS population includes those subjects all treated in TP2 who either undergo a CT or MRI scan with tumor assessment at 12 weeks (i.e. they have not discontinued treatment prior to 12 weeks) or those who have discontinued TP2 prior to 12 weeks solely due to documented disease progression. Radiographic disease progression and responses will be defined using RECIST 1.1 criteria:

Control Response(CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions. The appearance of new lesions is also considered progression.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD

The best overall response was the best response recorded from the start of Treatment Period 2 until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).To be assigned a status of CR or PR, tumor measurements were confirmed by repeat assessment performed at least four weeks after the criteria for response are first met. Best Overall Response (OR) was determined based on the following combinations of repeat assessments: CR + CR = CR, CR + PR= SD, PD or PR, CR + SD =SD, CR+ PD = SD, CR + NEW= SD, PR + CR= PR, PR + PR= PR, PR+ SD= SD, PR + PD= SD, PR+ NEW = SD.

Progressive Disease was assessed using RECIST Guideline (version 1.1) whereas at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Progression-free Survival (PFS) was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until disease progression or death from any cause, whichever occurs first. For the purpose of analysis of PFS, subjects with an unknown response were censored.

Stable Disease (SD) was assessed using RECIST Guideline (version 1.1) whereas neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Duration of Stable Disease was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until the criteria for disease progression were first met. For the purpose of analysis of Duration of SD, subjects who died before documented progressive disease were censored.

Once disease progression was documented in Treatment Period 2, subjects returned for the Safety Follow-up Visit four (4) weeks following the last treatment and continued to be followed for an additional 12-month period for overall survival. Overall Survival (OS) was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until the subject's death from any cause. For the purpose of analysis of OS, if a subject is alive at the date of last contact the subject was censored at that date of contact.

Xenetic Biosciences, Inc.

Treatment Period 1 (Progestin Monotherapy): During Treatment Period 1, all subjects determined to be PrR positive will receive progestin monotherapy, megestrol acetate, for up to 24 weeks. Subjects will have an MRI or CT scan after 12 and 24 weeks of progestin monotherapy, with response to treatment being assessed according to RECIST 1.1 criteria. All subjects that achieve disease control confirmed by tumor assessment after Treatment Period 1, will be ineligible to enter Treatment Period 2. These subjects will be terminated from the trial and treated according to local standards of practice, which may include continued progestin therapy.

Progestin Monotherapy

Treatment Period 2 (Combination Treatment): All subjects determined to be PrR negative at Screening and those who received at least 4 weeks of progestin monotherapy and who experienced disease progression at the conclusion of Treatment Period 1 will enter Treatment Period 2 of the study. During Treatment Period 2, subjects will receive Sodium Cridanimod in combination with continued progestin treatment, megestrol acetate. Subjects will receive treatment until disease progression as defined according to RECIST 1.1 criteria, with response assessments performed at 12-week intervals.

Sodium Cridanimod & Progestin Therapy

Subjects noted at Screening to have PrR (+) tumors were enrolled into Treatment Period 1 (TP1) receiving Progestin Monotherapy. Subjects noted to have Progressive Disease rolled into Treatment Period 2 (TP2) and received combination therapy of Sodium Cridanimod and Progestin. PrR (+) subjects that had Disease Control or Stable Disease after 24 weeks of Monotherapy treatment were not eligible to participate in TP2 and were discontinued.

PrR (+) Subjects

Subjects with PrR(-) tumors at screening will be enrolled directly into Treatment Period 2 (TP2) receiving combination therapy of Sodium Cridanimod and Progestin.

PrR(-) Subjects

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The study was discontinued early due to a change in development strategy and not due safety concern. No safety concerns were noted during the trial. This change in development strategy was the determining factor in the decision to discontinue the study. Because the study was terminated early, the planned analysis was not conducted, as full enrollment was not met.

Dr. Curtis Lockshin

Sodium Cridanimod and progestin therapy (megestrol acetate) combination

Sodium Cridanimod: The study will investigate the efficacy of Sodium Cridanimod in conjunction with progestin therapy in a population of subjects with endometrial cancer, who have failed progestin monotherapy or who have been identified as PrR negative.

progestin therapy: The study will investigate the use of progestin therapy in conjunction with Sodium Cridanimod

A total of 15 subjects entered Treatment Period 2, which included the 9 subjects who were PrR negative and the 6 subjects who were PrR positive and completed Treatment Period 1, and received treatment with Intramuscular (IM) sodium cridanimod in combination with oral progestin (megestrol acetate). 2 subjects were unevaluable and withdrew prior to meeting criteria for inclusion in FAS population.

Overall Disease Control (ODC) as Determined by Radiographic Imaging Measurements

A total of 15 subjects entered Treatment Period 2, which included the 9 subjects who were PrR negative and the 6 subjects who were PrR positive and completed Treatment Period 1, and received treatment with IM sodium cridanimod in combination with oral progestin (megestrol acetate). Four (4) subjects withdrew from the study prior to meeting evaluable criteria for ORR

Objective Response Rate (ORR)

001-15-01

001-30-01

001-39-05

001-45-02

001-48-01

001-01-03

001-39-07

001-39-08

001-43-01

001-45-01

001-47-03

A total of 15 subjects entered Treatment Period 2, which included the 9 subjects who were PrR negative and the 6 subjects who were PrR positive and completed Treatment Period 1, and received treatment with IM sodium cridanimod in combination with oral progestin (megestrol acetate). Four (4) subjects withdrew from the study prior to meeting evaluable criteria for PFS.

Progression-free Survival (PFS)

A total of 15 subjects entered Treatment Period 2, which included the 9 subjects who were PrR negative and the 6 subjects who were PrR positive and completed Treatment Period 1, and received treatment with IM sodium cridanimod in combination with oral progestin (megestrol acetate). Four (4) subjects withdrew from the study and 8 subjects did not meet the criteria to be evaluable for duration of SD.

Duration of Stable Disease

Fifteen (15) subjects who participated in Treatment Period 2 were eligible to be followed for OS; however, 4 of these subjects elected to not participate in the Follow-up Period because of withdrawal of consent (3 subjects) or other (1 subject, subject transferred to hospice). For the 11 subjects who participated in the Follow-up Period for OS, the time (in number of days) from the date of discontinuation to the time of death or last contact for survival information ranged from 32 to 457 days.

Overall Survival (OS)

PrR (-) Subjects

Safety Follow Up

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Medroxyprogesterone Acetate

Medroxyprogesterone

Sodium cridanimod in combination with megestrol acetate or medroxyprogesterone acetate. Treatment period is 12 months; patients will be followed for another 12 month period or to disease progression whichever occurs first.

Eligible patients will be enrolled into the study and administered sodium cridanimod (500 mg i.m./ twice a week) in combination with megestrol acetate (160 mg p.o./ day) or medroxyprogesterone acetate (200 mg p.o./ day).

Sodium cridanimod

Laura L. Douglass

This is an open label, multi-center, single arm phase II study. The study will investigate the efficacy of sodium cridanimod in conjunction with progestin therapy in a population of patients with recurrent or persistent PrR-negative endometrial cancer.

This is an open label, multi-center, single arm phase II study. The study will investigate the efficacy of sodium cridanimod in conjunction with progestin therapy in a population of patients with recurrent or persistent PrR-negative endometrial cancer.

Eligible patients will be enrolled into the study and administered sodium cridanimod in combination progestin therapy. Objective responses will be assessed at 12 week intervals. Patients will be treated for a 12 month period, followed by an additional 12 month follow up period or to disease progression whichever occurs first.

Important objectives of the study are to investigate the effect of sodium cridanimod in conjunction with progestin therapy on the level of PrR in tumor tissue and how this correlates to efficacy. To accomplish this objective, some of the patients enrolled in the study will undergo two tumor biopsies that will allow measurement of PrR levels in the tumor tissue before the treatment and after 4 weeks of therapy.

Virexxa (Sodium Cridanimod) w/Progestin Therapy in Pts w/Progesterone Receptor Neg Recurrent/Persistent Endometrial CA

A Phase II Study of Sodium Cridanimod in Conjunction With Progestin Therapy in Patients With Progesterone Receptor Negative Recurrent or Persistent Endometrial Carcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Endometrial Cancer Study for Women With Recurrent or Persistent Endometrial Cancer	NCT03077698	Endometrial Can...	Sodium Cridanim... progestin thera...	18 Years -	Xenetic Biosciences, Inc.
Virexxa (Sodium Cridanimod) w/Progestin Therapy in Pts w/Progesterone Receptor Neg Recurrent/Persistent Endometrial CA	NCT02064725	Recurrent or Pe...	Sodium cridanim...	18 Years -	Kevelt AS
Virexxa (Sodium Cridanimod) w/Progestin Therapy in Pts w/Progesterone Receptor Neg Recurrent/Persistent Endometrial CA	NCT02064725	Recurrent or Pe...	Sodium cridanim...	18 Years -	Kevelt AS

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