ALPN-202 With PD-1 Inhibition in Advanced Malignancies (NEON-2)

An Open-label Study of ALPN-202 Combined With PD-1 Inhibition in Subjects With Advanced Malignancies (NEON-2)

This is a cohort-based, open-label dose escalation and expansion study in adults with advanced solid tumors or lymphoma.

Study Overview

• Status: Terminated
• Conditions: Lymphoma; Advanced Solid Tumor
• Intervention / Treatment: Drug: ALPN-202; Drug: pembrolizumab KEYTRUDA®

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Investigational Site (213)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Investigational Site (212)
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Investigational Site (301)
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Investigational Site (203)
  • Texas
    • San Antonio, Texas, United States, 78229
      • Investigational Site (215)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult 18 to 80 years old at screening

• Pathologically confirmed, locally advanced or metastatic unresectable solid tumor, or Hodgkin or Non-Hodgkin lymphoma (including transformed lymphoma) of an acceptable histology:

  1. that is eligible for treatment with a PD-1 or PD-L1 inhibitor, or
  2. that is refractory or resistant to standard therapy, or
  3. for which standard or curative therapy is not available.
• Have received ≥ 2 prior systemic anti-cancer therapies (lymphoma subjects only)
• Protocol-defined measurable disease
• Available tumor biopsy representative of current disease
• ECOG performance status grade 0-1
• Life expectancy of ≥ 3 months
• Recovery to Grade ≤ 1 for any non-laboratory toxicity resulting from previous anticancer therapy prior to first dose of ALPN-202 (except alopecia, hearing loss, Grade ≤ 2 neuropathy, or endocrinopathy managed with replacement therapy)
• Adequate baseline hematologic, renal, hepatic and cardiac function

Exclusion Criteria:

• Any history of ≥ Grade 3 immune-related adverse event (irAE) requiring discontinuation from treatment or any history of a cardiovascular irAE
• Active or prior pneumonitis or interstitial lung disease
• Presence of any active central nervous system metastases
• Prior organ allograft or allogeneic hematopoietic stem cell transplantation
• Any other serious or uncontrolled health condition, which, in the opinion of the Investigator, would place the subject at undue risk from the study, impair the ability of the subject to receive protocol specified therapy, or interfere with the interpretation of study results.

• Receipt of any protocol-restricted therapy within the timeframes indicated:

  1. Checkpoint inhibitors, including PD-(L)1 (e.g., pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab), CTLA-4 (e.g., ipilimumab, tremelimumab), and Lag-3 (e.g., relatlimab), costimulatory agonists (including but not limited to CD28, CD134 (OX40), CD137 (4-1BB)): 3 months (135 days for atezolizumab)
  2. Chemotherapy, small molecule anticancer agents (e.g., kinase inhibitors), or radiation: 2 weeks
  3. Other monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, antibody-like drugs, cytokines, cell therapies, or radioimmunoconjugates: 4 weeks
• Any active, known, or suspected autoimmune disease
• Systemic treatment with corticosteroids (> 10 mg/day prednisone) or other immunosuppressive medication
• Any second malignancy active within the previous 3 years
• Active infection requiring therapy at the time of the first dose of ALPN-202.
• Known seropositivity for or active infection by human immunodeficiency virus, hepatitis B or C, or or Severe Acute Respiratory Syndrome Coronavirus 2.
• Known allergies, hypersensitivity, or intolerance to ALPN-202 or excipients in the drug product formulation.
• History of Grade 4 infusion-related, anaphylactic or allergic reaction to any previous Fc-based protein therapy.

• Any serious or uncontrolled cardiovascular condition, including but not limited to:

  1. Any history of myocarditis of any etiology
  2. History of New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, cerebrovascular accident, cardiac hospitalization, or other acute uncontrolled heart disease within 6 months of scheduled C1D1
  3. Left ventricular ejection fraction < 45% on screening echocardiogram
  4. Any clinically significant findings on screening EKG such as atrial or ventricular arrythmia (other than sinus tachycardia) or AV conduction abnormality such as left bundle branch block (such subjects may be enrolled after cardiology clearance and Medical Monitor approval)
• Has received prior radiotherapy within 2 weeks of start of study treatment, or have had a history of radiation pneumonitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Expansion; ALPN-202 + pembrolizumab KEYTRUDA®	Drug: ALPN-202; Various doses; Drug: pembrolizumab KEYTRUDA®; Varies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting Toxicities (DLTs)	Incidence of DLTs	Up to 6 weeks following study day 1
Adverse Events (AEs)	Type, incidence, severity, and seriousness of AEs	30 days after last dose of study drug
Laboratory Abnormalities	Type, incidence, and severity of laboratory abnormalities	Up to 30 days after last dose of study drug

Collaborators and Investigators

• Sponsor: Alpine Immune Sciences, Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Allison Naumovski, Ph.D., Alpine Immune Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2021
• Primary Completion (Actual): November 8, 2022
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: AIS-B02; MK-3475-D05/KEYNOTE-D05 (Other Identifier: Merk Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No