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Monoclonal Antibodies

APX005M + Nivolumab + Cabiralizumab for Melanoma

Phase 1

Waitlist Available

Led By Harriet Kluger, MD

Research Sponsored by Yale University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

RCC: Histologic or cytologically documented, locally advanced unresectable or metastatic RCC irrespective of histologic subtype

Biopsy proven metastatic melanoma, NSCLC or RCC whose disease has progressed on a prior regimen containing a PD-1 or PD-L1 inhibitor, without intervening therapy

Must not have

Current or history of clinically significant muscle disorders, recent unresolved muscle injury, or any condition known to elevate serum CK levels

A patient who has had prior immune therapy or chemotherapy, within 4 weeks prior to study Day 1, or who has not recovered from adverse events due to a previously administered agent will be excluded

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from study enrollment up to 6 years.

Awards & highlights

No Placebo-Only Group

Summary

This trial is a study to see if a new combination of drugs is safe and effective in treating advanced solid tumors. The study will enroll patients with melanoma, NSCLC, and RCC to see if the new combination is better than current treatments.

Who is the study for?

Adults with advanced melanoma, NSCLC, or RCC who have measurable lesions and normal organ/marrow function. They must not be pregnant, agree to contraception use, and can't have untreated brain metastases or certain active infections. Prior treatments should be completed within specific timeframes before starting the study drugs.

What is being tested?

The trial is testing a combination of three drugs: APX005M, Nivolumab, and Cabiralizumab in patients with advanced solid tumors. It includes an initial phase to find the best dose followed by a second phase focusing on each cancer type separately.

What are the potential side effects?

Potential side effects may include immune-related reactions affecting organs, infusion-related symptoms like allergic responses or skin reactions, fatigue from treatment burden on the body's systems, as well as possible complications from pre-existing conditions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney cancer is advanced, cannot be surgically removed, or has spread.

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My melanoma, NSCLC, or RCC has worsened after treatment with a PD-1 or PD-L1 inhibitor.

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I can provide tissue samples from at least one cancer site.

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My organs and bone marrow are functioning normally.

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I have a tumor that can be measured by CT or MRI.

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I can do most of my daily activities without help.

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I have advanced melanoma that cannot be surgically removed.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I don't have muscle disorders or recent muscle injuries that affect my CK levels.

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I haven't had immune therapy or chemotherapy in the last 4 weeks and have recovered from any side effects.

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I have been treated with CSF1R inhibitors or CD40 agonists before.

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I have brain metastases that have not been treated.

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I've had severe nerve, heart, or liver side effects from previous cancer immunotherapy.

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My cancer has spread to the lining of my brain and spinal cord.

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I have other active cancers besides the one being studied.

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I have HIV, HBV, or HCV infection.

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I do not have any open wounds or active skin infections.

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I am currently taking statins.

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I have lung inflammation that is not caused by an infection.

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I have uveal melanoma.

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I am not currently in any other clinical trials or have been in one within the last 4 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from study enrollment up to 6 years.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from study enrollment up to 6 years.

This trial's timeline: 3 weeks for screening, Varies for treatment, and from study enrollment up to 6 years. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety and Tolerability Measured by Assessing Serious Adverse Events (SAEs)and Adverse Events (AEs)

Safety and Tolerability Measured by Eastern Cooperative Oncology Group(ECOG) Performance Status

Secondary study objectives

Efficacy Measured by Objective Response Rate (ORR)

Other study objectives

Blood-based Pharmacodynamics (PD) of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by Circulating CD163+ Macrophages .

Blood-based Pharmacodynamics (PD) of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by Circulating CD8+ T Cells.

Cytokine-based Pharmacodynamic (PD) Biomarkers of APX005M, in Combination With Nivolumab and Cabiralizumab Assessed by CD40L Levels.

+11 more

Side effects data

From 2020 Phase 1 & 2 trial • 140 Patients • NCT03123783

50%

Pyrexia

50%

Nausea

43%

Dyspnoea

36%

Fatigue

36%

Chills

29%

Asthenia

29%

Alanine aminotransferase increased

29%

Gamma-glutamyltransferase increased

29%

Decreased appetite

29%

Pruritus

29%

Aspartate aminotransferase increased

21%

Malaise

21%

Oedema peripheral

21%

Abdominal pain upper

21%

Constipation

21%

Arthralgia

21%

Cough

14%

Chest discomfort

14%

Upper respiratory tract infection

14%

Infusion related reaction

14%

Blood alkaline phosphatase

14%

Pneumonia

14%

Abdominal pain

14%

Diarrhoea

14%

Dry mouth

14%

Vomiting

14%

Musculoskeletal pain

14%

Headache

14%

Somnolence

14%

Upper-airway cough syndrome

14%

Hyperhidrosis

Tremor

Deep vein thrombosis

Dysgeusia

Vocal cord paralysis

Blood alkaline phosphatase increased

Cardiac arrest

Pericardial effusion

Blood creatinine increased

Cancer pain

Brain oedema

Encephalitis autoimmune

Chronic obstructive pulmonary disease

Pulmonary embolism

Tachycardia

Hypothyroidism

Vision blurred

Weight decreased

Back pain

Musculoskeletal chest pain

Myalgia

Neck pain

Dizziness

Anxiety

Insomnia

Haemoptysis

Wheezing

Rash

Hypotension

Amylase increased

Night sweats

Urticaria

Toothache

Discomfort

Performance status decreased

Hypersensitivity

Asthenopia

Dry Eye

Eye Pain

Retinal exudates

Anorectal infection

Candida infection

Gingivitis

Herpes zoster

Pharygitis

Blood cortisol decreased

Blood glucose increased

Blood urea increased

Ostenonecrosis of jaw

Pain in jaw

Lethargy

Neuralgia

Depressive symptom

Disorientation

Lichenoid keratosis

Pruitus generalised

Lymph node pain

Ligament sprain

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 3A(Arm)/ PD1-NSCLC (Phase 2)

DL1 - APX005M 0.03 mg/kg + Nivolumab (Phase 1b Escalation)

DL2 - APX005M 0.1 mg/kg + Nivolumab (Phase 1b Escalation)

DL3 - APX005M 0.3 mg/kg + Nivolumab (Phase 1b Escalation)

Cohort 1(Arm)/ inNSCLC (Phase 2) - Includes Data From 1 Participant From DL3

Cohort 2(Arm)/ PD1-MM (Phase 2) - Includes Data From 2 Participants From DL3

Cohort 3B(Arm)/ PD1-NSCLC (Phase 2)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: Cohort 9 RCCExperimental Treatment3 Interventions

Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle.

Group II: Cohort 8 NSCLCExperimental Treatment2 Interventions

Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle.

Group III: Cohort 7 Advanced MelanomaExperimental Treatment3 Interventions

Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle.

Group IV: Cohort 6 Advanced Solid TumorsExperimental Treatment3 Interventions

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.3 mg/kg administered in 14 day cycles.

Group V: Cohort 5 Advanced Solid TumorsExperimental Treatment2 Interventions

Cabiralizumab 4mg/kg plus APX005M 0.3 mg/kg administered in 14 day cycles.

Group VI: Cohort 4 Advanced Solid TumorsExperimental Treatment3 Interventions

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.1 mg/kg administered in 14 day cycles.

Group VII: Cohort 3 Advanced Solid TumorsExperimental Treatment2 Interventions

Cabiralizumab 4mg/kg plus APX005M 0.1 mg/kg administered in 14 day cycles.

Group VIII: Cohort 2 Advanced Solid TumorsExperimental Treatment3 Interventions

Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.03 mg/kg administered in 14 day cycles.

Group IX: Cohort 1 Advanced Solid TumorsExperimental Treatment2 Interventions

Cabiralizumab 4mg/kg plus APX005M 0.03 mg/kg administered in 14 day cycles.