PDS01ADC Monotherapy and in Combination With M7824 in Advanced Kaposi Sarcoma
ConditionKaposi Sarcoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-99
SponsorNational Cancer Institute (NCI)
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Individuals with biopsy proven (confirmed in the Laboratory of Pathology [LP], CCR) Kaposi sarcoma (KS)
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
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.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
PDS01ADC
DrugAn 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.
M7824
Drug1200 mg administered IV every two weeks while on PDS01ADC.
Treatment groups
80 Participants
are divided into 3 treatment groupsGroup A: Arm 1/MonotherapyExperimental treatment 1 intervention
Group B: Arm 1a/Monotherapy ExpansionExperimental treatment 1 intervention
Group C: Arm 2/Combination therapyExperimental treatment 2 interventions
Trial outcomes
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.
Time frame
24 cycles of treatment, until confirmed progression, unacceptable toxicity or trial withdrawalSecondary outcomes
1
progression free survival
duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first
Time frame
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 years2
objective response rates
Percentage of participants with the best overall response of CR or PR to therapy
Time frame
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 years3
duration of response
the time criteria are met for CR or PR (whichever is recorded first) until the first date that participant no longer qualifies as a PR
Time frame
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 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov