Pixatimod (PG545) Plus Nivolumab in PD-1 Relapsed/Refractory Metastatic Melanoma and NSCLC and With Nivolumab and Low-dose Cyclophosphamide in MSS Metastatic Colorectal Carcinoma (mCRC)

NCT05061017 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 20-266
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goal of this trial is to assess clinical response to nivolumab and pixatimod, and, nivolumab, pixatimod and cyclophosphamide in three separate patient cohorts. Cohort 1: MSS mCRC in combination with low-dose cyclophosphamide, Cohort 2: PD-1 relapsed/refractory melanoma, and Cohort 3: PD-1 relapsed/refractory NSCLC.

Conditions

NSCLC; Metastatic Colorectal Carcinoma; Refractory Melanoma

Keywords

melanoma; PD-1/PD-L1 pathway; relapsed metastatic melanoma; refractory metastatic melonma; MSS Metastatic Colorectal Carcinoma; PD-1 R/R NSCLC; PD-1 R/R melanoma; MSS mCRC

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  Objective Response (rate) will be expressed as the percentage of patients with Complete Response (CR) + Partial Response (PR). Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD;Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease is neither \>30% shrinkage nor \>20% growth of tumor.

  Up to 26 months

• Objective Response Rate (ORR) - Combined Study Population

  Objective Response (rate) will be expressed as the percentage of patients with Complete Response (CR) + Partial Response (PR). Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD;Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease is neither \>30% shrinkage nor \>20% growth of tumor.

  Up to 26 months

Secondary Outcomes (19)

• Response Per Immune-related Response Criteria

  Up to 26 months

• Response Per Immune-related Response Criteria - Combined Study Population

  Up to 26 months

• Treatment-related Adverse Events

  Up to 26 months

• 6-month Progression-free Survival (PFS)

  Up to 6 months

• 1-year Progression-free Survival (PFS)

  Up to 12 months

Study Arms (2)

Pixatimod (PG545) + Nivolumab

EXPERIMENTAL

Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS CRC)

Drug: Pixatimod; Drug: Nivolumab

Pixatimod (PG545) + Nivolumab + cyclophosphamide

EXPERIMENTAL

Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks cyclophosphamide: 50 mg PO twice daily (Day 1-Day 7; Day 15-Day 21) with a 7-day drug free interval (Day 8-Day 14 and Day 22-Day 28) Cohort 2 (PD-1 R/R melanoma) and Cohort 3 (PD-1 R/R NSCLC)

Drug: Pixatimod; Drug: Nivolumab; Drug: Cyclophosphamide (low dose)

Interventions

Pixatimod DRUG

Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer.

Also known as: (PG545)

Pixatimod (PG545) + Nivolumab; Pixatimod (PG545) + Nivolumab + cyclophosphamide

Nivolumab DRUG

Nivolumab is approved by the FDA for the treatment of melanoma, non-small cell lung cancer (NSCLC), malignant pleural mesothelioma, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of head/neck, urothelial carcinoma, MSI-H colorectal cancer, hepatocellular carcinoma, gastric carcinoma and gastroesophageal junction (GEJ) cancer

Also known as: OPDIVO®

Pixatimod (PG545) + Nivolumab; Pixatimod (PG545) + Nivolumab + cyclophosphamide

Cyclophosphamide (low dose) DRUG

Cyclophosphamide is approved by the FDA for the treatment of acute lymphoblastic leukemia, acute monocytic leukemia, acute myeloid leukemia, breast cancer, chronic granulocytic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin lymphoma, multiple myeloma, mycosis fungoides, neuroblastoma, non-Hodgkin lymphoma, ovarian cancer, retinoblastoma. Low-dose (immunomodulatory) cyclophosphamide is being studied in combination with various types of immunotherapy including nivolumab and pembrolizumab

Pixatimod (PG545) + Nivolumab + cyclophosphamide

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with advanced/metastatic cutaneous melanoma, NSCLC or MSS mCRC who meet the following criteria will be enrolled in this study.
• Male participants:
• o A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP);OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• Cohort 1 (MSS mCRC)
• MSS is defined as 0-1 allelic shifts among 3-5 tumor microsatellite loci using a PCR-based assay or immunohistochemistry.
• Must have received prior therapy with a fluoropyrimidine, oxaliplatin, and irinotecan.
• Prior treatment with an anti-PD-1/anti-PD-L1 or anti-CTLA-4 antibody is not allowed.
• Prior treatment with BRAF/MEK inhibitor therapy (if BRAF mutated) and/or EGFR targeted antibody (if KRAS WT) are allowed.
• No more than 2 prior lines of therapy for metastatic disease.
• Adjuvant therapy will count as 1 prior line of therapy if received within the prior 6 months; but if not does not count towards prior line of therapy.
• PIV (pan-immune-inflammation) cutoff of 1200 obtained on labs obtained during Screening.

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• History of allergy and/or hypersensitivity and/or other clinically significant adverse drug reaction to heparin or other anti-coagulant agents, or to any monoclonal antibody.
• Use of heparin (including low-molecular weight heparin and/or fondaparinux) within 2 weeks prior to enrollment.
• o Patients who are currently receiving low-molecular weight heparin (or fondaparinux or other heparin product) for therapeutic anticoagulation may be enrolled if they have tested negative for anti-heparin antibodies at Screening.
• Has a diagnosis of immunodeficiency, immunosuppression and/or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Note: Subjects with autoimmune disorders of Grade 4 while on prior immunotherapy will be excluded. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤1 and the subject has been off systemic steroids at doses \>10 mg/d for at least 2 weeks.
• Active (i.e., symptomatic or growing) central nervous system (CNS) metastases.
• Note: Subjects with treated and stable CNS metastases are permitted to enroll. Stability for prior treated CNS disease should be assessed on a contrast-enhanced imaging study obtained no sooner than 14 days from data of definitive radiotherapy and/or surgery for CNS disease.
• Note: Subjects with leptomeningeal carcinomatosis are excluded.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone (or is being planned to undergo) potentially curative therapy.
• Has a systemic disease that requires systemic pharmacologic doses of corticosteroids greater than 10 mg daily prednisone (or equivalent).
• Note: Subjects who are currently receiving steroids at a dose of ≤10 mg daily do not need to discontinue steroids prior to enrollment.

Sponsors & Collaborators

• Diwakar Davar: lead
• Aculeus Therapeutics: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Lemech C, Dredge K, Bampton D, Hammond E, Clouston A, Waterhouse NJ, Stanley AC, Leveque-El Mouttie L, Chojnowski GM, Haydon A, Pavlakis N, Burge M, Brown MP, Goldstein D. Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors. J Immunother Cancer. 2023 Jan;11(1):e006136. doi: 10.1136/jitc-2022-006136.

  PMID: 36634920 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Melanoma

Interventions

PG 545; Nivolumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Barbara Stadterman, MPH, CCRP, Clinical Research Manager
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Diwakar Davar, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: September 29, 2021
• Study Start: December 9, 2021
• Primary Completion: February 5, 2024
• Study Completion: March 18, 2024
• Last Updated: March 7, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)