luveltamab tazevibulin (STRO-002)

P2/3, N=600, Recruiting, Sutro Biopharma, Inc. | Phase classification: P2 --> P2/3 | N=140 --> 600

P1/2, N=132, Recruiting, Tasly Pharmaceutical Group Co., Ltd

Part 1 is the dose-optimization stage, with ~50 subjects randomized 1:1 at 4.3 mg/kg Q3W or 5.2 mg/kg Q3W + prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg Q3W. Key exclusion criteria: primary platinum refractory disease and prior treatment with a FolRα ADC or ADC-containing tubulin inhibitor. Current Trial Status: Currently enrolling

Part 1 consists of a dose-optimization stage and will randomize ∼50 subjects 1:1 to the treatment of luvelta at 4.3 mg/kg Q3W or luvelta 5.2 mg/kg Q3W + prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg Q3W. Key inclusion criteria are progressive PROC, up to 3 prior regimens, TPS of ≥25% for FolRα expression, and measurable disease. Key exclusion criteria are primary platinum refractory disease and prior treatment with a FolRα ADC or ADC containing a tubulin inhibitor.

Preliminary data indicate that luvelta has a predictable and manageable safety profile with encouraging clinical activity in pts with recurrent/progressive FolRα expressing EEC. Luvelta warrants further development as a targeted agent for EEC.

P2, N=140, Recruiting, Sutro Biopharma, Inc. | Not yet recruiting --> Recruiting

In ovarian cancer, mirvetuximab soravtansine, an ADC targeting alpha-folate receptor (FRα), received US Food and Drug Administration (FDA) accelerated approval in November 2022 after data from the single-arm phase III SORAYA trial. A second ADC targeting FRα, STRO-002, received FDA fast track designation in August 2021. Multiple studies with upifitamab rilsodotin, an ADC comprising a NaPi2B-binding antibody, are underway. In cervical cancer, tisotumab vedotin, an ADC-targeting tissue factor, received FDA accelerated approval in September 2021 after the phase II innovaTV 204 trial...Trastuzumab-deruxtecan (T-DXd), an ADC targeting human epidermal growth factor receptor 2 (HER2), is currently approved for HER2-positive and HER2-low breast cancer and shows promise in endometrial cancer. Like all anticancer treatments, the decision for a patient to undergo therapy with an ADC is a personal choice that balances the potential benefits with the side effects and requires thorough and compassionate support of their physician and care team and shared decision making.

P2, N=140, Not yet recruiting, Sutro Biopharma, Inc.

For pts with a TPS >25% (n=35), the median prior lines of therapy was 2.5 (range 1-3), 69% had prior bevacizumab treatment, and 83% prior PARP inhibitor treatment. These dose expansion data confirm activity of luvelta at starting doses ranging from 4.3-5.2 mg/kg in recurrent OC with FolRα expression as low as TPS>25% and supports further clinical study in this population. The global phase 2/3 REFRaME registration study will evaluate luvelta in PROC pts with TPS >25%. Clinical trial information: NCT03748186.

In addition, combination treatment with carboplatin or Avastin further increased STRO-002 efficacy in xenograft models. The potent and specific pre-clinical efficacy of STRO-002 supports clinical development of STRO-002 for treating patients with FolRα-expressing cancers including ovarian, endometrial, and NSCLC. Phase I dose escalation for STRO-002 is in progress in ovarian cancer patients (NCT03748186).

Review of diagnostic genomic profile mid induction showed a BCR::ABL minor breakpoint fusion as well as CBF::GLIS fusion.The child began AML induction on COG AAML1831 trial randomized to the experimental arm with CPX-351 and gemtuzumab ozogamicin (GO). Due to lack of response to AML therapy at end of Induction (EOI) I, she was taken off protocol and started on modified ALL regimen for Induction II consisting of cytarabine, low dose weekly methotrexate and bimonthly peg-asparaginase with addition of an oral TKI, dasatinib...Given availability of FOLR1 directed ADC on single-patient compassionate use basis, patient received single agent STRO-001 on a bi-monthly basis...Long-term follow-up is required to assess durability of remission. Additional testing of this approach in a larger patient population is needed to determine the role of STRO-002 in this high-risk pediatric AML population.

In the 16 patients treated, 10 received STRO-002 as monotherapy, and 6 received combination with chemotherapy (fludarabine/cytarabine, decitabine, methotrexate (MTX), or dasatinib). STRO-002 has promising activity in relapsed/refractory CBF2AT3-GLIS2 AML, a disease that tends to be highly refractory to all standard-of-care (SOC) therapies. Further, STRO-002 is well tolerated as a monotherapy agent and in combination with SOC therapies. Patients with low tumor burden were more likely to achieve CR and transition to SCT, DLI and CAR-T.

No abstract available

No formal statistical hypothesis testing will be conducted in this study. This study is currently open for enrollment in the U.S.

We have demonstrated that STRO-002 in combination with avelumab in MC38-hFolRα-bearing mice significantly enhanced efficacy and durable anti-tumor immunity. In a NSCLC PDX model, a single dose of STRO-002 induced tumor regression and suppressed tumor growth for up to three months post-dose. In conclusion, the induction of ICD by STRO-002 has potential to increase anti-tumor activity in cancers with low FolRα expression.

P1, N=58, Recruiting, Sutro Biopharma, Inc.

STRO-002 is a novel FRα-targeting ADC with a promising emerging safety and efficacy profile and preliminary clinical benefit/disease control rate of 48% in patients with relapsed/refractory OC treated at ≥ 2.9 mg/kg. No ocular toxicity signals have been observed, suggesting potential differentiation from other FRα-targeting investigational therapies. Expansion cohorts in less heavily pre-treated patients are planned for 4Q20.

Cumulatively, these results suggest that STRO-002 synergizes with Avelumab to enhance anti-tumor response by inducing ICD in tumor cells, which in turn, promote T cell recruitment. These data support the rationale for combining STRO-002 with immune checkpoint inhibitors to potentially enhance their clinical efficacy.