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)

Inclusion Criteria: General Inclusion Criteria * 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. Cohort 2 (PD-1 R/R melanoma) * PD-1 refractory disease as defined as progression on treatment with anti-PD-(L)1 inhibitor administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria: * Receipt of at least 2 doses of an approved or investigational anti-PD-(L)1 inhibitor. * Demonstrated PD after anti-PD-(L)1 inhibitor as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression (as defined by the criteria in the sub-point below). * Progressive disease that has been documented within 12 weeks from the last dose of anti-PD-(L)1 inhibitor. * Progressive disease is determined according to iRECIST. * This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression. * Subjects who progressed on/within 3 months of adjuvant therapy with anti-PD-(L)1 inhibitor will be allowed; an adjuvant therapy will count as 1 prior line of therapy if received within the prior 6 months. * Prior treatment with an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody is allowed but not required. * Prior treatment with BRAF/MEK inhibitor therapy (if BRAF mutated) is allowed but not required. * No more than 5 prior lines of therapy. Cohort 3 (PD-1 R/R NSCLC) * PD-1 refractory disease as defined as progression on treatment with anti-PD-(L)1 inhibitor administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria: * Has received at least 2 doses of an approved or investigational anti-PD-(L)1 inhibitor. * Has demonstrated PD after anti-PD-(L)1 inhibitor as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression (as defined by the criteria in the sub-point below). * Progressive disease has been documented within 12 weeks from the last dose of anti-PD-(L)1 inhibitor. * Progressive disease is determined according to iRECIST. * This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression. * Subjects who progressed on/within 3 months of adjuvant therapy with anti-PD-(L)1 inhibitor will be allowed; an adjuvant therapy will count as 1 prior line of therapy if received within the prior 6 months. * Prior treatment with an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody is allowed but not required. * Prior treatment with BRAF/MEK inhibitor therapy (if BRAF mutated) must have received and progressed or have demonstrable intolerance to approved targeted therapy. * Patients with NSCLC with known oncogenic driver (including but not limited to EGFR, ALK, ROS, MET alterations) must have received and progressed past driver-specific therapy. * No more than 5 prior lines of therapy. Other Criteria * The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. * Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Have provided newly obtained core or excisional biopsy of a tumor lesion not previously irradiated to undergo tumor biopsy (core, punch, incisional or excisional). o Biopsy must meet minimal sampling criteria. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 28 days prior to the date of enrollment. * Adequate organ function. Screening labs obtained within 4 weeks of Cycle 1 day 1 * Proteinuria exceeding 1gram in a 24 hour period. * A pan-immune-inflammation (PIV) cutoff of 1200 (obtained on labs during Screening) * Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Exclusion Criteria: * 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. * Note: Subjects that require topical, ophthalmologic and inhalational steroids are not excluded from the study. * Note: Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome are not excluded from the study. * Note: Subjects who require active immunosuppression (greater than steroid dose discussed above) for any reason are excluded from the study. * Has evidence of interstitial lung disease or active, non-infectious pneumonitis. * Has an active infection requiring systemic therapy. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 26 weeks after the last dose of trial treatment. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). o Note: Subjects with HIV that is well controlled (undetectable viral load and CD4 count \>200 cells/mm3) on anti-retroviral therapy are permitted to enroll. * Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA \[qualitative\] is detected. o Note: Subjects with treated hepatitis B and/or C with no evidence of active infection may be enrolled. * Has a history of significant cardiac disease including but not limited to symptomatic congestive heart failure (New York Heart Association Class III/IV), uncontrolled hypertension (≥150/90mmHg) despite appropriate anti-hypertensive medication (patients with stably controlled hypertension are eligible), unstable angina pectoris or myocardial infarction (≤ 6 months prior to screening), uncontrolled cardiac arrhythmia, clinically significant cardiac valvopathy requiring treatment. * Receipt of live vaccine(s) within 30 days prior to the first dose of trial treatment. * Other uncontrolled intercurrent illness, including but not limited to, ongoing/active infection, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events and/or compromise the ability of the patient to give written informed consent.