Phase 1/2a/3 Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Advenchen Laboratories LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Jun 2022 → 31 Mar 2025

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Advenchen Laboratories, LLC

External identifiers

EU CT number

2024-516166-11-00

EudraCT number

2021-003871-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy between the Active Arm (AL3818 in combination with background chemotherapy) and Control Arm (background chemotherapy alone arm) as measured by the primary endpoint of Progression Free Survival (PFS). PFS will be evaluated by a blinded independent radiological review (BICR).

Secondary objectives 1

1. To evaluate the efficacy between the Active Arm and Control Arm as measured by the secondary endpoints of objective response rate (ORR), duration of response (DOR), and Overall Survival (OS). ORR will be evaluated by a blinded independent radiological review (BICR).

Conditions and MedDRA coding

Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Female = 18 years of age
2. Histologically proven diagnosis of: Phase III/Part 3: (1) Platinum-resistant (progression within 6 months after last platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer that meets one of the following criteria: i. Subject has received at least two prior lines of systemic therapy including a bevacizumab-containing regimen as standard of care ii. Subject has received at least two prior lines of systemic therapy, has not received a prior bevacizumab-containing regimen and is not eligible for a bevacizumab containing regimen based on Investigator’s assessment (2) Platinum-refractory (progression during first-line platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer after at least one prior line of systemic therapy (3) For groups 1-2 above: Subjects with positive deleterious or suspected deleterious, germline or somatic BRCA mutated status must have received a PARP inhibitor as a prior line of therapy. Histologic cell types eligible are squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma
3. Have measurable disease defined by RECIST 1.1 confirmed by CT or MRI scan within 28 days of enrollment.
4. Life expectancy of = 3 months at the time of enrollment.
5. Able to take orally administered study medication.
6. Have adequate baseline function and performance status within 28 days of enrollment: a. Bone marrow function: absolute neutrophil count (ANC) = 1,500/mm3, platelets =100,000/mm3 b. Renal function: creatinine = 1.5 x institutional upper limit normal (ULN) or if creatinine is >1.5 x ULN, creatinine clearance must be > 50 mL/min. c. Hepatic function: bilirubin = 1.5 x ULN or = 3.0 x ULN for subjects with Gilbert Syndrome; AST and ALT = 3.0 × ULN. d. Coagulation profile: international normalized ratio (INR) is = 1.5 and an aPTT or PTT <1.2 x ULN. e. ECOG performance = 2
7. Women of child-bearing potential must agree to use contraceptive measures starting 1 week before C1D1 until 4 weeks after the last dose of study treatment and have a negative serum pregnancy test within 28 days of enrollment.
8. Provide written informed consent and authorization permitting release of Protected Health Information.
9. Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures.

Exclusion criteria 23

1. Serious, non-healing wound, ulcer or bone fracture
2. Major surgical procedure within 28 days or minor surgical procedure performed within 7 days prior to C1D1 (a major surgical procedure is defined as requiring general anesthesia).
3. (Intentionally left blank)
4. Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
5. History or evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor; seizures not controlled with standard medical therapy; and history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within 6 months of enrollment. a. Subjects with metastatic CNS tumors may participate in this study if the subject is > 28 days from therapy completion (including radiation and/or surgery), is clinically stable at the time of study enrollment, and is not receiving corticosteroid therapy.
6. Proteinuria on urinalysis within 28 days of enrollment. Subjects discovered to have a urine protein of 1+ on dipstick or = 30 mg/dl at baseline should undergo a 24-hour urine collection and demonstrate < 1000 mg protein per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be <1.0 to allow participation in the study.
7. Clinically significant cardiovascular disease including uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to enrollment; New York Heart Association (NYHA) Grade II or greater congestive heart failure (Appendix E); serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease.
8. Women who are pregnant or nursing.
9. (Intentionally left blank)
10. Clinically significant, uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.
11. Hemoptysis within 3 months prior to enrollment.
12. Acute or chronic liver disease, active hepatitis A or B with known cirrhosis or liver dysfunction.
13. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment.
14. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or lifethreatening medical condition that required it.
15. Known history of human immunodeficiency virus infection (HIV).
16. Active bacterial infections requiring systemic antibiotics (excluding uncomplicated urinary tract infection).
17. Other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years prior to enrollment or whose previous cancer treatment contraindicates this protocol therapy.
18. History of non-malignant gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months prior to enrollment that in the opinion of the investigator may place the subject at risk of side effects on an anti-angiogenesis product.
19. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).
20. Intra-abdominal abscess within the last 3 months of enrollment.
21. Pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least five minutes apart, defined as systolic BP >160 mm Hg or diastolic BP >90 mm Hg pressure.
22. QTc > 470 msec on screening ECG per Fridericia’s formula.
23. History of or existing risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS) is defined as the median number of months from the date of randomization until the first documented sign of disease progression or death due to any causes, whichever occurs earlier. PFS will be evaluated by a blinded independent radiological review (BICR).

Secondary endpoints 3

1. Objective Tumor Response Rate (ORR) is defined as the proportion of subjects who achieve Complete Response (CR) or Partial Response (PR) as best responses according to RECIST 1.1. and duration of response. ORR will be evaluated by a blinded independent radiological review (BICR).
2. Duration of Response (DOR) is defined as median number of months from date of first documented objective response until first documented sign of disease progression or death due to any causes.
3. Overall Survival (OS) is defined as the time from randomization until death from any cause.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Advenchen Laboratories LLC

Sponsor organisation

Advenchen Laboratories LLC

Address

887 Patriot Drive Suite A

City

Moorpark

Postcode

93021-3355

Country

United States

Scientific contact point

Organisation

Advenchen Laboratories LLC

Contact name

Judy Chen

Public contact point

Organisation

Advenchen Laboratories LLC

Contact name

Judy Chen

Third parties 5

Locations

2 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications