PERELI - A phase 2, open label study of PEmigatinib and REtifanlimab in advanced dedifferentiated Liposarcoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Jun 2024 → ongoing

Decision date (initial)

2023-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Incyte Corporation · Sarkomföreningen · Fru Berta Kamprads Stiftelse

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate clinical benefit of retifanlimab and pemigatinib in patients with advanced DDLPS

Secondary objectives 4

1. To further evaluate clinical efficacy of retifanlimab and pemigatinib in DDLPS
2. To evaluate the safety and tolerability of pemigatinib and retifanlimab
3. To evaluate impact of treatment and disease status on quality of life
4. To evaluate the relationship between baseline and on-treatment biomarkers and clinical activity

Conditions and MedDRA coding

Dedifferentiated Liposarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. ● Be 18 years of age or above, on day of signing informed consent
2. ● Histologically confirmed DDLPS*. Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridization, polymerase chain reaction (PCR) or sequencing-based methods must be available.
3. ● Have the presence of at least 1 measurable lesion by CT per RECIST v1.1 that is considered non amenable to surgery or other curative treatments or procedures. Tumor lesions located in a previously irradiated area or in an area subjected to other loco-regional therapy are considered measurable if progression has been demonstrated in the lesion.
4. ● Be willing to provide tissue by core or excisional biopsy of a tumor lesion at the time points specified in the Trial Flow Chart. Archival tumor tissue can be used instead of pre-treatment biopsy. Biopsy will only be performed if the risk of complication is considered acceptable for the patient.
5. ● Have a performance status of 0-2 on the ECOG Performance Scale.

Exclusion criteria 15

1. ● Receipt of anticancer therapy within 28 days of the first administration of study treatment, with the exception of localized radiotherapy.
2. ● Toxicity of prior therapy that has not recovered to ≤ Grade 1 (with the exception of alopecia, peripheral neuropathy and anemia not requiring transfusional support), unless approved by the trial steering committee
3. ● Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
4. ● Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
5. ● Hypersensitivity to pemigatinib or retifanlimab or any of its excipients.
6. ● Has known active central nervous system (CNS) metastases and/or sarcomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include sarcomatous meningitis which is excluded regardless of clinical stability.
7. ● Has an active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 14 days before the first dose of study treatment.
8. ● Has an active infection requiring systemic antibiotics or antifungal or antiviral treatment within 7 days before first dose of study treatment.
9. ● Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
10. ● Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
11. ● Has received prior therapy with a selective FGFR inhibitor.
12. ● Has received a live vaccine within 30 days of planned start of study therapy.
13. • Has a history of calcium or phosphate homeostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance).
14. • Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug.
15. • Has a history of hypovitaminosis D currently requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-fee survival (PFS) at 24 weeks. PFS is defined as the time from the first dosing date to the date of the first objectively documented disease progression or death du to any cause, whichever occurs first. Disease progression based on tumor assessment (RECIST version 1.1 criteria).

Secondary endpoints 8

1. Objective response rate (ORR) defined as the percentage of patients achieving a confirmed complete or partial response, as defined by RECIST v. 1.1.
2. Overall survival (OS) is calculated as the time from date of start of the treatment to the date of death due to any cause.
3. Percentage of patients by Best Overall Response (BOR) according to RECIST v1.1. BOR is the best response (CR, PR, SD or PD) recorded from the start of the study treatment until disease progression.
4. Time to response (TTR), calculated as the time from the date of start of treatment until the first documented CR or PR.
5. Duration of response (DOR) is calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer.
6. Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) include all changes in laboratory values, vital signs, and assessment of physical, dermatological examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.
7. Changes in patient performance status (PS) from baseline in the Eastern Cooperative Oncology Group (ECOG) PS at 24 weeks.
8. Changes in Quality of life (QoL) from baseline assessed by EORTC QLQ-C30 questionnaire.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Helena Nyström

Public contact point

Organisation

Region Skane

Contact name

Helena Nyström

Third parties 1

Locations

3 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

Documents 6 files

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

Application history

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