A study to compare effectiveness and safety of a combination of vudalimab or pembrolizumab with chemotherapy in participants with advanced lung cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Xencor Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jun 2024 → 30 Dec 2025

Decision date (initial)

2024-05-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Xencor Inc.

External identifiers

EU CT number

2023-509644-10-00

ClinicalTrials.gov

NCT06173505

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

Part 1: To determine the RP2D of vudalimab in combination with chemotherapy based on safety and tolerability
Part 2: To compare PFS in subjects treated with vudalimab plus chemotherapy to those treated with pembrolizumab plus chemotherapy

Secondary objectives 2

1. Part 1 Secondary: To evaluate the antitumor activity of vudalimab in combination with chemotherapy in subjects with advanced NSCLC. Part 1 Secondary: To evaluate the pharmacodynamics of vudalimab in combination with chemotherapy. Part 1 Secondary: To characterize the PK of vudalimab
2. Part 2 Secondary: To compare the antitumor activity of vudalimab to pembrolizumab in combination with chemotherapy. Part2 Secondary: To compare OS in subjects treated with vudalimab plus chemotherapy to those treated with pembrolizumab plus chemotherapy. Part 2 Secondary: To examine the safety and tolerability of vudalimab in combination with chemotherapy relative to pembrolizumab plus chemotherapy. Part 2 Secondary: To evaluate the pharmacodynamics of vudalimab in combination with chemotherapy relative to pembrolizumab plus chemotherapy. Part 2 Secondary: To characterize the PK of vudalimab

Conditions and MedDRA coding

Advanced Non-small Cell Lung Cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Each subject must meet all of the following inclusion criteria to be enrolled in the study: 1. Able to provide written informed consent 2. Age ≥ 18 years 3. Histologically confirmed, locally advanced (unresectable) or metastatic nonsquamous NSCLC 4. Documented absence of tumor activating EGFR mutation and ALK gene and c-ros oncogene 1 (ROS1) rearrangements. Patients with unknown or indeterminate EGFR, ALK, or ROS1 status are excluded 5. Documented absence of alterations in any other actionable driver oncogenes for which there are locally approved targeted first-line therapies, based on testing conducted as part of standard local practice 6. PD-L1 IHC testing documenting TPS < 1% or between 1% and 49%
2. 7. No prior systemic treatment for advanced/metastatic NSCLC. Prior adjuvant, neoadjuvant, or chemoradiation/consolidation therapy is permitted, provided treatment was completed ≥ 12 months prior to development of metastatic disease 8. Measurable disease by RECIST 1.1 (note: lesions in a previously irradiated site are measurable if progression has been demonstrated in those lesions) 9. Adequate archival formalin-fixed paraffin-embedded (FFPE) tumor block(s)/slides 10. ECOG performance status score of 0 or 1 11. Life expectancy ≥ 3 months
3. 12. Adequate organ function, as indicated by the following laboratory values • Hemoglobin ≥ 9 g/dL, with no transfusion for ≥ 4 weeks • Absolute neutrophil count ≥ 1.5 × 109/L • Platelet count ≥ 100 × 109/L • Alanine aminotransferase (ALT) < 3 × upper limit of normal (ULN) for subjects without liver metastases or < 5 × ULN for subjects with liver metastases • Total bilirubin ≤ 1.5 × ULN, unless there is prior diagnosis and documentation of ongoing hemolysis or Gilbert’s syndrome • Thyroid stimulating hormone (TSH) within the normal range with or without replacement therapy (note, if TSH is not within the normal range, the patient may be eligible if reflex testing of total triiodothyronine [T3] or free T3 and free thyroxine [T4] are within the normal range) • Estimated creatinine clearance ≥ 45 mL/min using the Cockcroft-Gault formula 13. Women of childbearing potential must agree to use a highly effective method of birth control and abstain from breastfeeding during the study, for 120 days after the last dose of vudalimab or pembrolizumab, and for 180 days after the last dose of chemotherapy • Women are considered to be of childbearing potential unless it is documented that they are over the age of 60, OR postmenopausal by history with no menses for 1 year and confirmed by follicle-stimulating hormone (FSH; using local reference ranges), OR have a history of hysterectomy and/or bilateral oophorectomy, OR have a history of bilateral tubal ligation • Highly effective methods of birth control include hormonal birth control (oral, intravaginal, or transdermal), or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or intrauterine), intrauterine devices (IUDs), intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner (provided partner is the sole sexual partner and there has been a medical assessment of surgical success), or sexual abstinence
4. 14. Fertile male subjects must be willing to practice a highly effective method of birth control (ie, vasectomy or a condom in combination with double-barrier methods, spermicide, hormonal birth control, or an IUD [nonhormonal] used by the partner) and abstain from sperm donation during the study, for 120 days after the last dose of vudalimab or pembrolizumab, and 180 days after the last dose of chemotherapy 15. Able and willing to complete the study according to the study schedule

Exclusion criteria 2

1. Subjects who meet any of the following criteria will be excluded from the study: 1. Participation in a study of an investigational agent or device within 4 weeks prior to planned start of study treatment 2. Expected to require any other anticancer therapy while on study 3. Major surgery within 3 weeks of planned start of study treatment 4. Have known active central nervous system metastases and/or carcinomatous meningitis. Patients with treated brain metastases may participate, provided they are radiologically stable (ie, are without evidence of progression for ≥ 4 weeks by repeat imaging performed during the screening period, are clinically stable, and are without requirement of steroid treatment for ≥ 7 days prior to the first dose of study treatment) 5. For patients treated in the neoadjuvant or adjuvant setting: • Failure to recover from any other cancer therapy-related toxicity (other than immune-related toxicity) related to previous anticancer treatment to ≤ Grade 2 • History of a life-threatening (Grade 4) immune-mediated adverse event associated with prior administration of an immunotherapy agent • Failure to recover from any immunotherapy-related toxicity from prior cancer therapy to ≤ Grade 1, except that subjects are eligible if a previous immunotherapy-related endocrinopathy is medically managed with hormone replacement therapy only or if immune-mediated alopecia has not resolved • Known history of severe hypersensitivity to monoclonal antibody therapy • Known history of hypersensitivity to platinum-based chemotherapy or pemetrexed 6. Active known or suspected autoimmune disease 7. Has any condition requiring systemic treatment with corticosteroids, (> 10 mg daily prednisone equivalents) , or other immunosuppressive medications within 14 days prior to first dose of study drug (except that inhaled or topical corticosteroids or brief courses of corticosteroids given for prophylaxis of contrast dye allergic response are permitted) 8. Receipt of an organ allograft
2. 9. Evidence of any serious bacterial, viral, parasitic, or systemic fungal infection within the 30 days prior to the first dose of study drug 10. Interstitial lung disease that is symptomatic or a history of pneumonitis requiring systemic glucocorticoid treatment. Lymphangitic spread of NSCLC is not an exclusion. 11. Receipt of a live-virus vaccine within 30 days prior to first dose of study drug 12. Known human immunodeficiency virus (HIV) positive with CD4+ T-cell (CD4+) count < 350 cells/μL, or an HIV viral load greater than 400 copies/mL, or a history of an acquired immunodeficiency syndrome-defining opportunistic infection within the past 12 months, or not on established antiretroviral therapy (ART) for at least 4 weeks prior to initiation of study drug dosing. 13. Positive test for hepatitis C RNA 14. Positive test for hepatitis B surface antigen (hBsAg) or hepatitis B core antibody (hBcAb); a patient whose hBsAg is negative and hBcAb is positive may be enrolled if a hepatitis B virus (HBV) DNA test is negative and the subject is retested for HbsAg and HBV DNA every 2 months 15. History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) other than NSCLC, that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study evaluations, procedures, or completion 16. Positive pregnancy test (ie, human chorionic gonadotropin); planning to become pregnant while enrolled in the study, or breastfeeding for up to 120 days after the last dose of vudalimab or pembrolizumab, and 180 days after the last dose of chemotherapy. 17. Prisoner or involuntarily incarcerated

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1 Primary - Incidence of TEAEs Treatment-related adverse events leading to discontinuation of treatment
2. Part 2 Primary - PFS (time from randomization to disease progression per RECIST 1.1 or death, whichever comes first)

Secondary endpoints 2

1. Part 1 Secondary - ORR, as determined by the Investigator (per RECIST 1.1), and DOR. Part 1 Secondary - Changes in ctDNA over time. Part 1 Secondary - Cmax, Ctrough, and other key exposure parameters.
2. Part 2 Secondary - ORR (RECIST 1.1), DCR and DOR. Part 2 Secondary - OS (time from randomization to death from any cause). Part 2 Secondary - Incidence of TEAEs. Part 2 Secondary - Changes in ctDNA over time. Part 2 Secondary - Cmax, Ctrough and other key exposure parameters.

Investigational products

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

Test 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Xencor Inc.

Sponsor organisation

Xencor Inc.

Address

111 West Lemon Avenue

City

Monrovia

Postcode

91016-2809

Country

United States

Scientific contact point

Organisation

Xencor Inc.

Contact name

Jolene Shorr

Public contact point

Organisation

Xencor Inc.

Contact name

Jolene Shorr

Third parties 11

Locations

7 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Results and documents

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

Documents 65 files

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

Application history

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