Part C of A Phase 1b/2a Study of LY2880070 in Patients with Advanced or Metastatic Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Esperas Pharma Inc., Esperas Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Nov 2023 → 14 Apr 2025

Decision date (initial)

2023-08-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Dose response, Pharmacodynamic, Safety

to assess the safety and tolerability of LY + GEM in patients with BRCA1/2 wildtype HGSOC

Secondary objectives 1

1. to evaluate the efficacy of LY + GEM in patients with BRCA1/2 wildtype HGSOC

Conditions and MedDRA coding

Advanced or Metastatic Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Ambulatory patients ≥ 18 years of age
2. Are recovered or recovering from the acute adverse effects of any chemotherapy, biologic therapy, immunotherapy, cancer-related hormonal therapy, therapy with investigative agents, or radiotherapy (≤Grade 1), with the exception of Grade 2 alopecia or neuropathy
3. Have received at least 2 but no more than 4 prior systemic therapies for locally advanced or metastatic disease (e.g., hormonal, cytotoxic, etc.), at least one of which should be platinum-based.
4. Patients who have had major surgery must be fully recovered and ≥4 weeks postoperative prior to enrolling on study
5. Males and females with reproductive potential must agree to use highly effective, medically approved contraceptives and females must avoid egg cell donation during the study and for 6 months following the last dose of study treatment. Highly effective contraceptives for females includes: – combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal – progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable – intrauterine device – intrauterine hormone-releasing system – bilateral tubal occlusion – vasectomised partner –sexual abstinence
6. All females of child-bearing potential females must have had a negative serum pregnancy test result ≤ 28 days prior to the first dose of study treatment and must have had a negative urine pregnancy test result ≤1 day prior to the first dose of study treatment. For the purpose of this document, a female is considered of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
7. Patients must have documented progressive disease after the last treatment regimen and tumor lesions that are considered measurable by RECIST v1.1. Lesion(s) must be accurately measurable in at least one dimension, and for which the longest diameter is a minimum of: a) a. 10 mm by CT scan (CT scan slice thickness no greater than 5 mm), or b) 10 mm caliper measurement by clinical exam
8. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy and no standard therapy would confer clinical benefit to the patient.
9. PART C: 20. Patients must have histologically confirmed high grade serous ovarian carcinoma as follows: • Must have failed, but not be refractory to, prior platinum therapy. Refractory is defined as no response to treatment or progression during or within 1 month of platinum-based therapy and platinum refractory patients will be excluded. Patients who are platinum sensitive or resistant, meaning that the patient had disease recurrence more than 1 month after platinum-based therapy, are eligible for this study. • Must have the ability to tolerate GEM in the opinion of the investigator. • May have received GEM as previous therapy if it was not discontinued due to toxicity or progressive disease. Must have completed the last GEM-containing regimen at least 12 months prior to first dose of combination therapy on this study. • Must have archival tissue block available that meets the requirements for Next Generation Sequencing (NGS) (refer to the Laboratory Manual) or tumor accessible for fresh biopsy. Alternatively, a report from previous NGS testing may be submitted upon discussion with the sponsor. • Must be confirmed BRCA 1/2 wild-type.
10. Have given written informed consent prior to any study-specific procedures
11. Are reliable and willing to make themselves available for the duration of the study, and are willing to follow study procedures
12. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
13. Have an estimated life expectancy of ≥12 weeks
14. Are able to swallow capsules
15. Have adequate organ function including: a) Hematologic: ANC ≥1.5 x 109/L, platelets ≥100 x 109/L, and hemoglobin ≥ 90 g/L. Patients may receive red blood cell transfusions to achieve this hemoglobin level at the discretion of the investigator, so long as transfusions are discontinued ˃7 days prior to initiation of study treatments. b) Hepatic: Bilirubin ≤1.5 times ULN, ALT and AST ≤2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling ≤5 times ULN are acceptable. c) Renal: Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2
16. Have discontinued cytotoxic therapy, biologic therapy, immunotherapy, and cancer-related hormonal therapy at least 21 days prior to study enrollment (6 weeks for mitomycin-C or nitrosoureas), and have discontinued radiotherapy at least 21 days prior to study enrollment
17. Have discontinued drugs with moderate inhibition of CYP2D6 or greater at least 5 half-lives prior to study enrollment

Exclusion criteria 13

1. Have received treatment with an investigational drug which has not received regulatory approval for any indication within 21 days of study treatment with LY
2. Have already participated in this study
3. Have had radiation therapy to >25% of bone marrow
4. For Parts B and C, patients who have a history of another active cancer within the past year except cervical cancer in situ, in situ carcinoma of the bladder, basal cell carcinoma of the skin or another in situ carcinoma that is considered cured by the investigator
5. Have medical conditions that, in the opinion of the investigator, would preclude participation in this study (e.g., a new or preexisting skin disorder that would make IV administration and/or toxicity assessments difficult)
6. Have symptomatic central nervous system (CNS) metastasis. Patients with treated CNS metastasis are eligible, provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastasis is not required
7. Have a history of major organ transplant (e.g., heart, lungs, liver, and kidney)
8. Females who are pregnant or nursing
9. Have known positive test results of human immunodeficiency virus, or have chronic active hepatitis A, B or C.
10. Have QTcB >470 msec (female) or >450 msec (male), a history of congenital long QT syndrome, or other conduction abnormality that in the opinion of the investigator would preclude safe participation in this study
11. Have had an autologous or allogeneic bone marrow transplant
12. Are currently enrolled in another clinical study of an investigational medicinal product
13. Have hypersensitivity to the active substance of gemcitabine or to any of its excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety (treatment emergent adverse events, serious adverse events, and clinical abnormalities per Common Terminology Criteria for Adverse Event)

Secondary endpoints 1

1. overall response rate, disease control rate

Investigational products

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

Test 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Esperas Pharma Inc.

Sponsor organisation

Esperas Pharma Inc.

Address

1610-1255 Robert-Bourassa Boulevard

City

Montreal

Postcode

H3B 3X3

Country

Canada

Scientific contact point

Organisation

Esperas Pharma Inc.

Contact name

Caroline Fortier

Public contact point

Organisation

Esperas Pharma Inc.

Contact name

Darcy Vincett

Esperas Pharma Inc.

Sponsor organisation

Esperas Pharma Inc.

Address

1610-1255 Robert-Bourassa Boulevard

City

Montreal

Postcode

H3B 3X3

Country

Canada

Locations

2 EU/EEA countries · 6 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 8 files

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

Application history

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