Trial Outcomes & Findings for 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) (NCT NCT05061017)

Last Updated: 2025-03-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Up to 26 months

Results posted on

2025-03-07

Participant Flow

Participant milestones

Participant milestones
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 and Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Overall Study STARTED	5	8
Overall Study COMPLETED	5	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pixatimod (PG545) + Nivolumab n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS CRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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	Total n=13 Participants Total of all reporting groups
Age, Continuous	58.00 years STANDARD_DEVIATION 13.45 • n=5 Participants	71.75 years STANDARD_DEVIATION 8.26 • n=7 Participants	66.46 years STANDARD_DEVIATION 12.19 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 26 months

Population: Treated patients who were radiologically evaluable.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Objective Response Rate (ORR) Stable Disease (SD)	40 percentage of patients	37.5 percentage of patients
Objective Response Rate (ORR) Progressive Disease (PD)	60 percentage of patients	62.5 percentage of patients

PRIMARY outcome

Timeframe: Up to 26 months

Population: Treated patients who were radiologically evaluable.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Objective Response Rate (ORR) - Combined Study Population Stable Disease (SD)	38 percentage of patients	—
Objective Response Rate (ORR) - Combined Study Population Progressive Disease (PD)	62 percentage of patients	—

SECONDARY outcome

Timeframe: Up to 26 months

Population: Treated patients who were radiologically evaluable for iRECIST.

irCR (Complete Response):Disappearance of non-nodal lesions. All pathologic lymph nodes \<10 mm (2 consecutive measures ≥4 weeks apart); irPR (Partial Response):≥30% decrease from baseline (2 consecutive measures ≥4 weeks apart); irPD (Progressive Disease):≥20% increase from nadir and ≥5mm (2 consecutive measures ≥4 weeks apart); irSD (Stable Disease): Not sufficient decrease for PR, nor sufficient increase for PD; irPR (Progressive Disease): Disappearance of all non-nodal lesions.All pathologic lymph nodes \<10 mm (Non-Target Lesions:Any other than disappearance of all non-nodal lesions and reduction of pathologic lymph nodes \<10 mm). Baseline tumor burden: sum of single diameters (short axis for nodal lesions, longest diameter for other lesions) for target lesions. In subsequent scans, the diameters of new measurable lesions are added to the tumor burden. Re-treatment: ≤5 target lesions (=/≠ original lesions) are selected and a new baseline tumor burden will be established.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Response Per Immune-related Response Criteria Unknown	0 percentage of patients	12.5 percentage of patients
Response Per Immune-related Response Criteria iStable Disease	40.0 percentage of patients	37.5 percentage of patients
Response Per Immune-related Response Criteria iUProgressive Disease	60.0 percentage of patients	50.0 percentage of patients

SECONDARY outcome

Timeframe: Up to 26 months

Population: Treated patients who were radiologically evaluable for iRECIST.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Response Per Immune-related Response Criteria - Combined Study Population Unknown	8 percentage of patients	—
Response Per Immune-related Response Criteria - Combined Study Population iStable Disease	38 percentage of patients	—
Response Per Immune-related Response Criteria - Combined Study Population iUProgressive Disease	54 percentage of patients	—

SECONDARY outcome

Timeframe: Up to 26 months

Population: All treated patients.

Distinct number of patients with (all-grade) related adverse events (AE), serious adverse events (SAE) and dose-limiting toxicities (DLT) if any in each cohort. Toxicity events were evaluated by NCI Common Terminology for Adverse Events (CTCAE v5.0).

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Treatment-related Adverse Events Weight loss	0 participants	1 participants
Treatment-related Adverse Events Anemia	1 participants	0 participants
Treatment-related Adverse Events Lymphocyte count decreased	2 participants	0 participants
Treatment-related Adverse Events Neutrophil count decreased	1 participants	0 participants
Treatment-related Adverse Events Alanine aminotransferase increased	0 participants	1 participants
Treatment-related Adverse Events Alkaline phosphatase increased	0 participants	1 participants
Treatment-related Adverse Events Anorexia	0 participants	1 participants
Treatment-related Adverse Events Arthralgia	0 participants	1 participants
Treatment-related Adverse Events Aspartate aminotransferase increased	0 participants	1 participants
Treatment-related Adverse Events Amylase increased	0 participants	1 participants
Treatment-related Adverse Events Fatigue	0 participants	2 participants
Treatment-related Adverse Events Hyperglycemia	0 participants	1 participants
Treatment-related Adverse Events Rash maculo-papular	0 participants	1 participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: Treated patients who were radiologically evaluable.

Percentage of patients who remain progression-free from the initial date of treatment until 6 months afterwards, with progression defined by RECIST v 1.1. 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.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
6-month Progression-free Survival (PFS)	20 percentage of patients Interval 1.0 to 58.0	13 percentage of patients Interval 1.0 to 42.0

SECONDARY outcome

Timeframe: Up to 12 months

Population: Treated patients who were radiologically evaluable.

Percentage of patients who remain progression-free from the initial date of treatment until 1 year afterwards, with progression defined by RECIST v 1.1. 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.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
1-year Progression-free Survival (PFS)	0 percentage of patients Upper and lower bound of CI not reached due to low number of events.	13 percentage of patients Interval 1.0 to 42.0

SECONDARY outcome

Timeframe: Up to 24 months

Population: Treated patients who were radiologically evaluable.

Percentage of patients who remain progression-free from the initial date of treatment until 2 years afterwards, with progression defined by RECIST v 1.1. 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.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
2-year Progression-free Survival (PFS)	0 percentage of patients Upper and lower bound of CI not reached due to low number of events.	0 percentage of patients Upper and lower bound of CI not reached due to low number of events.

SECONDARY outcome

Timeframe: Up to 27 months

Population: Treated patients who were radiologically evaluable.

Progression-free survival is the time measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression), whichever occurs first, with progression defined by RECIST v 1.1. 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.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Progression-free Survival (PFS)	2.00 months Interval 1.0 to Upper bound of CI not reached due to low number of events.	2.00 months Interval 1.0 to Upper bound of CI not reached due to low number of events.

SECONDARY outcome

Timeframe: Up to 6 months

Population: Treated patients who were radiologically evaluable.

Percentage of patients with Progression-free survival (measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression)), whichever occurs first, with progression defined by RECIST v 1.1. 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.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Progression-free Survival (PFS) - Combined Study Population	15 percentage of patients Interval 2.0 to 39.0	—

SECONDARY outcome

Timeframe: Up to 12 months

Population: Treated patients who were radiologically evaluable.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Progression-free Survival (PFS) - Combined Study Population	15 percentage of patients Interval 2.0 to 39.0	—

SECONDARY outcome

Timeframe: Up to 24 months

Population: Treated patients who were radiologically evaluable.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Progression-free Survival (PFS) - Combined Study Population	0 percentage of patients Upper and lower bound of CI not reached due to low number of events.	—

SECONDARY outcome

Timeframe: Up to 27 months

Population: Treated patients who were radiologically evaluable.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Progression-free Survival (PFS) - Combined Study Population	2.00 months Interval 1.0 to 4.0	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: All trial participants.

Percentage of patients that remain alive from the start of treatment until death from any cause at one year.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
6-month Overall Survival (OS)	75 percentage of patients Interval 13.0 to 96.0	50 percentage of patients Interval 15.0 to 77.0

SECONDARY outcome

Timeframe: Up to 12 months

Population: All trial participants.

Percentage of patients that remain alive from the start of treatment until death from any cause at one year.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
1-year Overall Survival (OS)	0 percentage of patients Upper and lower bound of CI not reached due to low number of events.	19 percentage of patients Interval 1.0 to 54.0

SECONDARY outcome

Timeframe: Up to 24 months

Population: All trial participants.

Percentage of patients that remain alive from the start of treatment until death from any cause at two years.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 Participants 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
2-year Overall Survival (OS)	0 percentage of patients Upper and lower bound of CI not reached due to low number of events.	0 percentage of patients Upper and lower bound of CI not reached due to low number of events.

SECONDARY outcome

Timeframe: Up to 6 months

Population: All trial patients.

Percentage of patients that remain alive from the start of treatment until death from any cause at 6 months.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Overall Survival (OS) - Combined Study Population	61 percentage of patients Interval 29.0 to 81.0	—

SECONDARY outcome

Timeframe: Up to 12 months

Population: All trial patients.

Percentage of patients that remain alive from the start of treatment until death from any cause at 12 months.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Overall Survival (OS) - Combined Study Population	13 percentage of patients Interval 1.0 to 43.0	—

SECONDARY outcome

Timeframe: Up to 24 months

Population: All trial patients.

Percentage of patients that remain alive from the start of treatment until death from any cause at 24 months.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Overall Survival (OS) - Combined Study Population	0 percentage of patients Not reached due to low number of events.	—

SECONDARY outcome

Timeframe: Up to 27 months

Population: All trial patients.

The median length of time (estimated) from the start of treatment that patients remain alive, until death from any cause.

Outcome measures

Outcome measures
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=13 Participants Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Overall Survival (OS) - Combined Study Population	11.00 months Interval 4.0 to 12.0	—

SECONDARY outcome

Timeframe: At baseline, 4 weeks

Population: Data not collected.

Percent change in cellular frequency from baseline in the CD8+ T cell infiltrate and/or NK cell in the tumor and TME in tumor biopsies at treatment timepoints.

Outcome measures

Outcome data not reported

Adverse Events

Pixatimod (PG545) + Nivolumab - Cohort 1

Serious events: 1 serious events

Other events: 5 other events

Deaths: 3 deaths

Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3

Serious events: 3 serious events

Other events: 8 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Pixatimod (PG545) + Nivolumab - Cohort 1 n=5 participants at risk Pixatimod : 25 mg IV, weekly Nivolumab: 480 mg IV, Q4 weeks Cohort 1 (MSS MCRC) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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	Pixatimod (PG545) + Nivolumab + Cyclophosphamide - Cohort 2 & Cohort 3 n=8 participants at risk 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) Pixatimod: Pixatimod is an investigational drug that is being evaluated in studies involving melanoma, non-small cell lung cancer, and microsatellite stable colorectal cancer. Nivolumab: 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 Cyclophosphamide (low dose): 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
Cardiac disorders Sinus tachycardia	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Ear and labyrinth disorders Vertigo	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Gastrointestinal disorders Nausea	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
General disorders Fatigue	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Investigations Alanine aminotransferase increased	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	20.0% 1/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Nervous system disorders Dizziness	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	12.5% 1/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	25.0% 2/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.
Vascular disorders Thromboembolic event	0.00% 0/5 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.	25.0% 2/8 • Adverse Events and Serious Adverse Events occurring up to 26 months from the date start of treatment.

Other adverse events

Additional Information

Barbara Stadterman, MPH, CCRP, Clinical Research Manager

UPMC Hillman Cancer Center

Phone: 4126475554

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place