PDS01ADC Monotherapy and in Combination With M7824 in Advanced Kaposi Sarcoma

NCT04303117 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 20006120-C-0061
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Kaposi sarcoma (KS) tumors grow on the skin, lymph nodes, lungs, bone, and gastrointestinal tract. KS often affects people with immune deficiencies, such as among people living with HIV or those with prior history of transplant. Researchers want to see if 2 non-chemotherapy drugs can help people with KS. PDS01ADC triggers the immune system to fight tumors. M7824 blocks the pathways that cancer cells use to stop the immune system from fighting tumors. Objective: To learn if giving PDS01ADC alone or with M7824 could help the immune system fight KS tumors. Eligibility: People 18 and older with KS that has been treated with chemotherapy or immunotherapy Design: Participants will be screened with some or all of the following: medical history physical exam chest X-ray computed tomography scan blood and urine tests electrocardiogram and echocardiogram skin KS lesion biopsy lung exam gastrointestinal exam All participants will get PDS01ADC every 4 weeks for up to 96 weeks (or 24cycles). It is injected under the skin. Some participants will also get M7824 every 2 weeks for up to 96 weeks (or 24cycles). It is given through a plastic tube that is put in an arm vein. Participants will complete questionnaires about how KS affects their quality of life. Their KS lesions will be measured and photographed. They will repeat some of the screening tests. They will give saliva samples or additional tissue samples. They will have a lung function test. Their ability to perform their normal activities will be assessed. The treatment duration is up to 96 weeks (or 24cycles) with an option to take PDS01ADC and/or M7824 until the KS tumors are not responding, or you develop unacceptable side effects. Participants will have follow-up visits 7 and 30 days after treatment ends, then every 3 to 6 months for the next 18 months, then once a year for 3 years.

Conditions

Kaposi Sarcoma

Keywords

Immune Therapy; AIDS; HIV; Immunocytokine

Outcome Measures

Primary Outcomes (1)

• safety, tolerability and activity of PDS01ADC alone or in combination with M7824

  The fraction of participants with toxicity noted at each dose level will be reported by grade and type of toxicity identified. Maximum tolerated dose will also be reported.

  24 cycles of treatment, until confirmed progression, unacceptable toxicity or trial withdrawal

Secondary Outcomes (3)

• progression free survival

  every 3 months for the first 6 months after completion of therapy, then every six months for the next 18 months, and then annually for a total of 3 years

• objective response rates

  every 3 months for the first 6 months after completion of therapy, then every six months for the next 18 months, and then annually for a total of 3 years

• duration of response

  every 3 months for the first 6 months after completion of therapy, then every six months for the next 18 months, and then annually for a total of 3 years

Study Arms (3)

Arm 1/Monotherapy

EXPERIMENTAL

Treatment with PDS01ADC at de-escalating doses if necessary

Drug: PDS01ADC

Arm 1a/Monotherapy Expansion

EXPERIMENTAL

Treatment with PDS01ADC at MTD

Drug: PDS01ADC

Arm 2/Combination therapy

EXPERIMENTAL

Treatment with PDS01ADC at MTD and M7824 at a fixed dose

Drug: PDS01ADC; Drug: M7824

Interventions

M7824 DRUG

1200 mg administered IV every two weeks while on PDS01ADC.

Arm 2/Combination therapy

PDS01ADC DRUG

An initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks and at an MTD dose with M7824 on day 1 of a 28-day cycle.

Arm 1/Monotherapy; Arm 1a/Monotherapy Expansion; Arm 2/Combination therapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals with biopsy proven (confirmed in the Laboratory of Pathology \[LP\], CCR) Kaposi sarcoma (KS)
• KS requiring systemic therapy, with or without history of prior KS therapy:
• T1 KS or T0 KS sufficiently widespread that systemic therapy is advisable, or KS affecting quality-of-life due to local symptoms or psychological distress
• OR,
• KS with an inadequate response to liposomal doxorubicin, paclitaxel, other systemic chemotherapy (either progressive disease or stable disease after 3 or more cycles) or immunotherapy (progressive disease)
• A wash-out period off treatment of 2 weeks from last chemotherapy and 4 weeks from last immunotherapy, other systemic treatment with a biologic agent, or monoclonal antibody therapy will be required in individuals with prior KS therapy.
• Resolution of toxicity from prior therapy to \<= Grade 1.
• At least five measurable cutaneous KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion.
• Measurable disease by the criteria proposed by the AIDS Clinical Trials Group (ACTG) Oncology Committee for KS
• HIV positive or negative.
• ART for HIV+ individuals for 8 or more weeks prior to entry with an HIV viral load of \<400 copies/ml at screening and CD4+ T cell count of \>= 50 cells/microliter as this may be expected if individuals have received several courses of chemotherapy.
• Age \>=18 years.
• ECOG performance status \<=2 (Karnofsky \>=60%).
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count \>=1,000/mcL

You may not qualify if:

• Receiving any other investigational agents.
• Pregnant individuals are excluded from this study as the effects of PDS01ADC and M7824 have potential teratogenic or abortifacient effects.
• Severe KS (such as symptomatic pulmonary KS) that could be life threatening if it progressed over 2-4 weeks
• Actively bleeding sites caused by visceral KS.
• Unwilling to accept blood products as medically indicated
• Actively bleeding and/or requiring transfusions in the 2 weeks preceding study entry.
• History of bleeding, diathesis, or recent major bleeding events within a period of 4 weeks considered by the investigator as high risk for investigational drug treatment.
• Any active or recent history (symptomatic in the last 3 months) of a known or suspected autoimmune disease (with the exception of diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment) or recent history of a syndrome that required systemic corticosteroids (10mg daily prednisone or equivalent) or immunosuppressive medications except inhaled steroids and adrenal replacement steroids doses up to 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Uncontrolled opportunistic infections
• Active multicentric Castleman disease
• Individuals with primary effusion lymphoma
• History of malignant tumors other than KS, unless:
• In complete remission for \>= 3 years from the time complete remission was first documented or
• Resected basal cell or squamous cell carcinoma of the skin or
• In situ cervical or anal dysplasia

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Kaposi; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Ramya M Ramaswami, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irene B Ekwede, R.N.

CONTACT

(240) 760-6126; irene.ekwede@nih.gov

Ramya M Ramaswami, M.D.

CONTACT

(240) 506-1088; ramya.ramaswami@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2020
• First Posted: March 10, 2020
• Study Start: July 13, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-04-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI

Locations

US (1)