ASTRAEA: ReinvigorAting ReSponse To ImmunotheRApy in MEtAstatic TNBC With Combination Myeloid Inhibition and Radiation
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorStephen Shiao
About this trial
Open label, single-arm, prospective therapeutic trial. Pembrolizumab (MK-3475), 200 mg IV Q3W starting at C1D1/Week 1 for up to 2 years, until disease progression, or treatment intolerance. RT, 8 Gy x 3 fractions over 3 consecutive days at C1D8/Week 2; Axatilimab (SNDX-6352; INCA034176), 1 mg/kg, IV, Q2W starting 1 week post- RT C1D15/Week 3 until disease progression or treatment intolerance.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years at the time of consent.
Patients with metastatic or locally recurrent TNBC who received prior immunotherapy in any setting (curative or advanced/metastatic).
Have ≥2 measurable, non-osseous, non-hepatic recurrent or metastatic lesions. Of these lesions, at least one is indicated for radiation therapy and at least one will not be irradiated to be used to determine response. Notes on lesions: patients are still eligible if they have liver or bone lesions, so long as at least 2 measurable lesions are non-osseous, non-hepatic recurrent or metastatic per above criterion.
Histologically or cytologically-confirmed TNBC, defined as ER <10%, PR <10%, HER2-negative by ASCO CAP guidelines. Note: HER2 0-2+ IHC is allowed (i.e., if FISH-negative, this is still considered HER2-negative).
Disqualifiers
Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Has a known history of active TB (Bacillus Tuberculosis).
Trial design
Design model
Single group
Treatments tested in this trial
Pembrolizumab
DrugPembrolizumab (MK-3475), 200 mg IV Q3W starting at C1D1/Week 1 for up to 2 years, until disease progression, or treatment intolerance.
Radiotherapy
RadiationRT, 8 Gy x 3 fractions over 3 consecutive days at C1D8/Week 2;
Axatilimab
DrugAxatilimab (SNDX-6352; INCA034176), 1 mg/kg, IV, Q2W starting 1 week post- RT C1D15/Week 3 until disease progression or treatment intolerance.
Treatment groups
34 Participants
are divided into 1 treatment groupGroup A: Pembrolizumab, Radiotherapy, AxatilimabExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Overall Response Rate (ORR)
The proportion of patients with confirmed PR or CR per RECIST v1.1, assessed from the start of study treatment (defined as from first dose of pembrolizumab) for up to two years. ORR in the non-targeted, unirradiated lesion(s) as defined by CR or PR per iRECIST. Objective response will be assessed separately in all sites that are not irradiated.
Time frame
From start of study treatment until subject proceeds to standard of care treatment, up to 2 years.Secondary outcomes
1
Number of Adverse Events Related to Study Treatment
To determine the safety, toxicity, and tolerability of the combination in recurrent or metastatic TNBC. Safety, toxicity, and tolerability of the combination will be assessed by the number of adverse events related to study treatment per NCI's CTCAE v5.0 from start of study treatment up to 90 days post end of study treatment.
Time frame
From start of study treatment up to 90 days post end of study treatment.2
Progression-free survival (PFS)
To assess progression-free survival (PFS). Assessed from the start of study treatment until documented progression, or death due to any cause.
Time frame
Up to 2 years post end of study treatment.3
Overall Survival (OS)
To assess overall survival (OS). Assessed from the start of study treatment until death due to any cause.
Time frame
Up to 2 years post end of study treatment.4
Duration of Response (DoR)
To assess duration of response (DoR). Assessed from the start of study treatment until documented progression, or death due to any cause.
Time frame
Up to 2 years post end of study treatment.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Stephen Shiao
Lead sponsor
Cedars-Sinai Medical Center
Sponsor institution
Merck Sharp & Dohme LLC
Collaborator
Incyte Corporation
Collaborator
Source ClinicalTrials.gov
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