A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 (SAR445710) in Subjects With Metastatic or Locally Advanced Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kadmon Corporation LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 1 Dec 2023

Decision date (initial)

2023-07-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi Research & Development

External identifiers

EU CT number

2022-503080-15-00

WHO UTN

U1111-1279-2406

ClinicalTrials.gov

NCT04242147

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacogenomic, Pharmacokinetic, Others, Pharmacodynamic

- Dose escalation (bi-weekly and weekly monotherapy dosing cohorts): To determine the safety/tolerability and the maximum tolerated dose (MTD) of KD033 (SAR445710) at different dosing regimens in participants with confirmed advanced and/or metastatic solid tumors.
- Expansion cohort: To confirm the safety/tolerability and find early efficacy signal of KD033 (SAR445710) in monotherapy

Secondary objectives 3

1. To evaluate efficacy: best overall response (BOR) and duration of response (DOR) (escalation and expansion)
2. To characterize pharmacokinetic (PK) profile of KD033 (SAR445710) (escalation and expansion)
3. To evaluate the potential immunogenicity KD033 (SAR445710) (escalation and expansion)

Conditions and MedDRA coding

Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically or cytologically confirmed/documented advanced and/or metastatic solid tumor with at least one tumor lesion of location accessible to biopsy per clinical judgement of treating physician.
2. Participants must be willing to provide a tumor biopsy at the following time points: Pre-treatment and at Cycle 4, Day 1. All other study eligibility criteria must be met before any biopsy sample is obtained.
3. Measurable disease at baseline per RECIST v1.1 guidelines.
4. Life expectancy of at least 3 months.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ≤ 1.
6. Adequate organ and bone marrow functions.
7. All toxicities related to prior radiotherapy, chemotherapy, or surgical procedure must have recovered to baseline or Grade ≤ 1 based on NCI-CTCAE v5.0 except alopecia (any grade), Grade 2 peripheral neuropathy and adverse events that are clinically non-significant or stable on supportive care.
8. All participants, male and female, who are not surgically sterilized or postmenopausal must agree to use "highly effective methods of contraception" during the study and for at least 60 days after the last dose of KD033 (SAR445710).
9. Women of childbearing potential must have a negative pregnancy test within 7 days prior to KD033 (SAR445710) treatment.
10. Ability to understand the purpose of the study, provide signed and dated informed consent from the participant/legal representative prior to performing any protocol-related procedures and able to comply with the study procedures and any locally required authorization.

Exclusion criteria 22

1. Use of immunotherapy, biological therapy, cytokine therapy < 21 days prior to the first dose of study drug.
2. Use of immunomodulating agents < 21 days prior to the first dose of study drug.
3. Use of chemotherapy and approved tyrosine kinase inhibitor (TKI) therapy < 14 days prior to the first dose of study drug.
4. Anti PD-L1 or anti PD-1 therapy < 6 weeks prior to the first dose of study drug.
5. Radiotherapy within 14 days before the start of trial treatment (prior diagnostic biopsy is permitted), with the exception of palliative radiation as described: patients assigned to radiotherapy require at least 1 additional lesion that can be safely irradiated while sparing the index lesion(s), and for which radiation at the limited, palliative doses contemplated would be considered medically appropriate; The lesion should be causing some signs or symptoms (e.g., tumor-related pain), for which radiation is indicated per the physician's standard clinical practice.
6. Use of any investigational drug or have major surgery within 28 days before the start of trial treatment
7. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required systemic immunosuppressive treatments.
8. Systemic therapy with immunosuppressive agents including corticosteroids within 14 days before the start of trial treatment with the exception of corticosteroid replacement therapy for adrenal insufficiency
9. Rapidly progressive disease which, in the opinion of Investigator, may predispose to inability to tolerate treatment or trial procedure.
10. History or clinical evidence of central nervous system primary tumors or metastases including leptomeningeal metastases unless they have been previously treated, demonstrated no progression at least 1 months, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before Screening. Participants with suspected brain metastases at Screening should undergo a CT/MRI of the brain prior to study entry.
11. Receipt of any organ transplantation including hematopoietic cell transplantation.
12. Has a paraneoplastic syndrome of autoimmune nature.
13. History of interstitial lung disease or severe obstructive pulmonary disease.
14. Clinically significant cardiovascular/cerebrovascular disease.
15. QTc(F) interval > 450 ms for men or > 470 ms for women)
16. Left ventricular ejection fraction (LVEF) < 50% as measured by an echocardiogram (ECHO).
17. Active infection requiring therapy.
18. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding.
19. Pregnant or breast-feeding women
20. Known severe hypersensitivity reactions to monoclonal antibodies, any history of or recent (within 6 months) of anaphylaxis
21. Vaccine administration within 4 weeks of investigational drug administration.
22. Vaccination with live vaccines while on trial is prohibited. Administration of inactivated vaccines like inactivated influenza vaccines is allowed. COVID-19 vaccines are approved to be administered prior to KD033 (SAR445710) administration and during the treatment phase, however, it is preferred to not vaccinate during the 28-day DLT period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Occurrence of Dose Limiting Toxicities (DLTs): To evaluate the number of participants who experienced DLTs during the dose escalation phase
2. Treatment Emergent Adverse Events (TEAEs) and Treatment-related AEs by Severity: To evaluate the number of TEAEs and treatment-related AEs by severity for all dose groups/cohorts according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)

Secondary endpoints 5

1. Best Overall Response (BOR): To evaluate the best overall response from study treatment according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria per Investigator assessment
2. Duration Of Response (DOR): To evaluate the duration of response from study treatment according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria per Investigator assessment
3. Exploration of KD033 (SAR445710) Pharmacokinetic (PK) Profile - AUC: Area under the concentration versus time curve (AUC)
4. Exploration of KD033 (SAR445710) Pharmacokinetic (PK) Profile - Cmax: Maximum plasma concentration observed (Cmax)
5. Exploration of Anti-KD033 (SAR445710) Antibodies: To evaluate serum titers and assessment of neutralization of anti-KD033 (SAR445710) antibodies using blood samples collected during the dose escalation and dose expansion phases

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kadmon Corporation LLC

Sponsor organisation

Kadmon Corporation LLC

Address

55 Corporate Drive

City

Bridgewater

Postcode

08807-1265

Country

United States

Scientific contact point

Organisation

Kadmon Corporation LLC

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Kadmon Corporation LLC

Contact name

Clinical Sciences and Operations

Third parties 7

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

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 4 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