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ASTRAEA: ReinvigorAting ReSponse To ImmunotheRApy in MEtAstatic TNBC With Combination Myeloid Inhibition and Radiation

Phase 2
Not yet recruiting
Conditions
TNBC - Triple-Negative Breast Cancer
Breast Cancer
Interventions
Registration Number
NCT07015853
Lead Sponsor
Stephen Shiao
Brief Summary

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.

Detailed Description

Checkpoint blockade-mediated immunotherapy (IO) is an emerging cornerstone in the treatment of triple negative breast cancer (TNBC) in both the metastatic and curative intent settings. Initial studies of IO monotherapy in heavily pretreated metastatic TNBC were disappointing with low objective response rate (ORR) (5.3%: KEYNOTE-086, KEYNOTE-119) and no effect in OS (1-3). However, recent studies in patients with previously untreated metastatic TNBC, showed IO combinations with chemotherapy were associated with improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone in patients with "PD-L1 positive" disease (IMpassion130 and KEYNOTE-355) (4-7). Nonetheless, nearly half of patients on IMpassion130 had grade 3 or higher toxicity, leading to a discontinuation rate of 16.9%, and over 70% of all patients on first-line IO containing regimens will experience disease progression within one year. Based on these data, IO-containing regimens have become the standard-of-care treatment option for metastatic TNBC, albeit with a high failure rate and a non-trivial toxicity profile. Second line antibody-drug conjugate Sacituzumab govitecan while also improving response in metastatic TNBC still has 85% of patients fail at 1 year (ASCENT, Bardia NEJM 2021). Therefore, novel strategies that augment IO-enhanced tumor-specific responses and limit treatment-associated toxicities are critically important in TNBC. Lastly, radiotherapy (RT), commonly used in palliation of metastatic TNBC, is a potent modulator of the immune response, and can produce responses in unirradiated tumors in combination with IO (8-11).

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
34
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Pembrolizumab, Radiotherapy, AxatilimabPembrolizumabPembrolizumab (MK-3475), 200 mg IV Q3W starting at C1D1/Week 1 for up to 2 years, until disease progression, or treatment intolerance. Radiotherapy, 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.
Pembrolizumab, Radiotherapy, AxatilimabRadiotherapyPembrolizumab (MK-3475), 200 mg IV Q3W starting at C1D1/Week 1 for up to 2 years, until disease progression, or treatment intolerance. Radiotherapy, 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.
Pembrolizumab, Radiotherapy, AxatilimabAxatilimabPembrolizumab (MK-3475), 200 mg IV Q3W starting at C1D1/Week 1 for up to 2 years, until disease progression, or treatment intolerance. Radiotherapy, 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.
Primary Outcome Measures
NameTimeMethod
Overall Response Rate (ORR)From start of study treatment until subject proceeds to standard of care treatment, up to 2 years.

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.

Secondary Outcome Measures
NameTimeMethod
Number of Adverse Events Related to Study TreatmentFrom start of study treatment up to 90 days post end of 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.

Progression-free survival (PFS)Up to 2 years post end of study treatment.

To assess progression-free survival (PFS). Assessed from the start of study treatment until documented progression, or death due to any cause.

Overall Survival (OS)Up to 2 years post end of study treatment.

To assess overall survival (OS). Assessed from the start of study treatment until death due to any cause.

Duration of Response (DoR)Up to 2 years post end of study treatment.

To assess duration of response (DoR). Assessed from the start of study treatment until documented progression, or death due to any cause.

Trial Locations

Locations (1)

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
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