VX15/2503 in Combination With Avelumab in Advanced Non-small Cell Lung Cancer

NCT03268057 | Completed Phase 1 FDA Drug

• 1 other identifier: VX15/2503-04
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of IV administration of VX15/2503 in combination with a fixed dose of avelumab in patients with advanced non-small cell lung cancer. The dose escalation portion of the study will determine the maximum tolerated dose (MTD) of VX15/2503 administered in combination with avelumab.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-Small-Cell Lung; Carcinoma; Advanced; VX15/2503; Semaphorin 4D; SEMA4D; safety tolerability; pharmacokinetics; monoclonal antibody; IO Failure; Immunotherapy Failure; Decline Chemo

Outcome Measures

Primary Outcomes (2)

• Dose Escalation Phase: Number of subjects with dose-limiting toxicities (DLT)s at each dose level

  DLTs will be described and graded according to the Common Terminology Criteria Adverse Events version 4.03 (CTCAE v4.03) and according to the specific MedRA terms from immune mediated AEs

  21 Days for Each Escalation Phase

• Dose Expansion Phase: Frequency and type of adverse events (AE)s

  Safety assessments will be performed on a regular basis using physical examination, spontaneous AE reporting, scheduled and unscheduled laboratory assessments, and other diagnostic evaluations as indicated. Adverse events will be reported using the Common Terminology Criteria Adverse Events version 4.03 (CTCAE v4.03).

  2 Years

Secondary Outcomes (10)

• Dose Expansion Phase: Objective Response (OR)

  2 Years

• Dose Expansion Phase: Duration of Response (DoR)

  2 Years

• Dose Expansion Phase: Progression Free Survival (PFS)

  2 Years

• Dose Expansion Phase: Peak serum concentration (Cmax) of VX15/2503 and avelumab

  2 Years

• Dose Expansion Phase: Area under the serum concentration versus time curve (AUC) of VX15/2503 and avelumab

  2 Years

Study Arms (1)

VX15/2503 + avelumab

EXPERIMENTAL

VX15/2503 at a concentration of 5 mg/kg, 10 mg/kg or 20 mg/kg with a fixed dose of avelumab at 10 mg/kg, administered intravenously on a bi-weekly dosing cycle.

Drug: VX15/2503 + avelumab

Interventions

VX15/2503 + avelumab DRUG

Dose escalation will begin at 5 mg/kg of VX15/2503 and will increase up to 20 mg/kg with a constant dose of avelumab at 10 mg/kg. A recommended phase II dose of VX15/2503 will be determined and then utilized in the expansion phase with 10 mg/kg of avelumab.

VX15/2503 + avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years.
• Signed informed consent prior to the performance of any study-specific procedures, including fresh tumor biopsies.
• Histologically or cytologically proven advanced (stage IIIB/IV) NSCLC subjects. Subjects in the Dose Escalation Phase must be immunotherapy naïve.
• i. Subjects in the Dose Escalation Phase must have either progressed on or declined standard first-line therapy. Subjects with fewer than 3 lines of prior palliative systemic anti-cancer therapy are eligible.
• ii. Subjects in the Dose Expansion Phase must have progressed on a minimum of 2 cycles of standard of care platinum-based chemotherapy with or without immunotherapy, standard of care immunotherapy without chemotherapy or must have declined standard of care first-line treatment options. Subjects with fewer than 3 lines of prior palliative systemic anti-cancer therapy are eligible.
• Subjects previously treated with systemic adjuvant/neoadjuvant therapy, other than immunotherapy are also eligible for the Dose Escalation Phase. Subjects previously treated with standard of care systemic adjuvant/neoadjuvant therapy are also eligible for the Dose Expansion Phase.
• Measureable disease as defined by the RECIST 1.1.
• Availability of archival or fresh tumor specimen that is suitable for analysis. Acceptable samples must have been acquired using core needle biopsy or excisional biopsy. Samples that were acquired using fine needle aspiration are not acceptable.
• Tumor lesion accessible for biopsy after the start of treatment. (Note: this lesion should be separate from measurable lesions that will be used for response assessment.)
• ECOG performance status (PS) score 0-1.
• Left ventricular ejection fraction \> 50%
• Tumors lack activating epidermal growth factor receptor (EGFR) mutations, ROS-1, or ALK rearrangement (no EGFR or ALK testing is required if a subject has a KRAS mutation or squamous cell histology)..
• Has adequate bone marrow, renal and hepatic function based upon laboratory tests as follows:
• Absolute neutrophil count \> 1500/µL
• Platelet count \> 100 x 103/µL

You may not qualify if:

• Prior therapy with any antibody or drug targeting T-cell coregulatory proteins (immune checkpoints), such as PD-1, PD-L1, or cytotoxic T lymphocyte antigen-4 in the Dose Escalation Phase only.
• Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on Investigator's judgment are acceptable.
• Concurrent anticancer treatment within 28 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy \[with the exception of palliative bone directed radiotherapy\]; immune therapy, or cytokine therapy, except for erythropoietin.
• Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy); or use of any investigational drug within 28 days before the start of trial treatment.
• Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily). Note: Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤10 mg per day of prednisone or equivalent.
• Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years (with the exception of adequately treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least 2 years prior to study entry and the subject was deemed to have been cured with no additional therapy required or anticipated to be required.
• Rapidly progressive disease disease (i.e. disease progression before or at the time of first tumor assessment, 8 - 12 weeks after initiation of systemic anti-cancer therapy).
• ECOG performance status score ≥ 2.
• Women who are pregnant or breastfeeding.
• History of pneumonitis or other interstitial lung disease
• Active or history of any autoimmune disease including colitis and inflammatory bowel disease (subjects with diabetes Type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies.
• Vaccination within 4 weeks of the first dose of avelumab and while on study is prohibited except for administration of inactivated vaccines (e.g. inactivated influenza vaccines).
• Significant acute or chronic infection including, among others: Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as, HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV DNA or HBV core antibody positive alone with reflex to positive HBV DNA or positive HCV antibody with reflex to positive HCV RNA).
• Central nervous system malignancy, the known presence of untreated or symptomatic CNS metastases. Subjects with treated brain metastasis must be stable and off steroids and anti-convulsants for at least 1 month prior to the start of study treatment. Subjects with suspected brain metastases at Screening should have a CT/MRI of the brain prior to study entry.
• A history of hypersensitivity to other humanized monoclonal antibodies.

Sponsors & Collaborators

• Vaccinex Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (11)

Highlands Oncology Group, PA

Fayetteville, Arkansas, 72703, United States

Location

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Northwell Health Cancer Institute

Lake Success, New York, 11042, United States

Location

University of Rochester

Rochester, New York, 14604, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Related Publications (4)

• Patnaik A, Weiss GJ, Leonard JE, Rasco DW, Sachdev JC, Fisher TL, Winter LA, Reilly C, Parker RB, Mutz D, Blaydorn L, Tolcher AW, Zauderer M, Ramanathan RK. Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors. Clin Cancer Res. 2016 Feb 15;22(4):827-36. doi: 10.1158/1078-0432.CCR-15-0431. Epub 2015 Oct 7.

  PMID: 26446947 BACKGROUND

• Evans EE, Jonason AS Jr, Bussler H, Torno S, Veeraraghavan J, Reilly C, Doherty MA, Seils J, Winter LA, Mallow C, Kirk R, Howell A, Giralico S, Scrivens M, Klimatcheva K, Fisher TL, Bowers WJ, Paris M, Smith ES, Zauderer M. Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and Enhances Response to Other Immunomodulatory Therapies. Cancer Immunol Res. 2015 Jun;3(6):689-701. doi: 10.1158/2326-6066.CIR-14-0171. Epub 2015 Jan 22.

  PMID: 25614511 BACKGROUND

• Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litiere S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EGE; RECIST working group. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar;18(3):e143-e152. doi: 10.1016/S1470-2045(17)30074-8. Epub 2017 Mar 2.

  PMID: 28271869 BACKGROUND

• Shafique MR, Fisher TL, Evans EE, Leonard JE, Pastore DRE, Mallow CL, Smith E, Mishra V, Schroder A, Chin KM, Beck JT, Baumgart MA, Govindan R, Gabrail NY, Spira AI, Seetharamu N, Lou Y, Mansfield AS, Sanborn RE, Goldman JW, Zauderer M. A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2021 Jul 1;27(13):3630-3640. doi: 10.1158/1078-0432.CCR-20-4792. Epub 2021 Apr 5.

  PMID: 33820783 DERIVED

Related Links

• Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors.
• Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and Enhances Response to Other Immunomodulatory Therapies

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• John E Leonard, PhD

  Vaccinex Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A dose escalation phase based on the use of a 3 + 3 design and treament of up to 6 subjects in each of three VX15/2503 dose levels; a fixed dose of avelumab will be employed. Once the recommended phase two dose is determined, subjects will receive that dose of VX15/205 combined with avelumab moving forward.

Study Record Dates

• First Submitted: August 11, 2017
• First Posted: August 31, 2017
• Study Start: October 5, 2017
• Primary Completion: September 9, 2020
• Study Completion: September 10, 2020
• Last Updated: May 2, 2022

Record last verified: 2022-04

Locations

US (11)