First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
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| ClinicalTrials.gov Identifier: NCT05768139 |
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Recruitment Status :
Recruiting
First Posted : March 14, 2023
Last Update Posted : May 16, 2024
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Sponsor:
Scorpion Therapeutics, Inc.
Information provided by (Responsible Party):
Scorpion Therapeutics, Inc.
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Brief Summary:
Study STX-478-101 is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 in participants with advanced solid tumors with certain mutations.
Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors and breast cancer; Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with breast cancer.
Each study part will include a 28-day screening period, followed by treatment with STX-478 monotherapy or combination therapy.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer Gynecologic Cancer HNSCC Solid Tumors, Adult | Drug: STX-478 Drug: Fulvestrant | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 400 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors |
| Actual Study Start Date : | April 17, 2023 |
| Estimated Primary Completion Date : | February 28, 2027 |
| Estimated Study Completion Date : | February 28, 2029 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
Drug Information
available for:
Fulvestrant
| Arm | Intervention/treatment |
|---|---|
Experimental: Part 1.1: Dose Escalation (Advanced Solid Tumors and Breast)
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Drug: STX-478
STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor. |
Experimental: Part 1.2-DE: Dose expansion at MTD
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Drug: STX-478
STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor. |
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Experimental: Part 1.2-DS: RP2D Selection (Breast)
Recommended Phase 2 dose (RP2D) Cohort A1: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations. |
Drug: STX-478
STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor. |
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Experimental: Part 1.3: RP2D Expansion (Breast)
Cohort A1: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.
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Drug: STX-478
STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor. |
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Experimental: Part 2.1: RP2D Selection
Cohort B: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.
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Drug: STX-478
STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor. Drug: Fulvestrant Fulvestrant will be administered according to local labeling.
Other Name: Faslodex |
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Experimental: Part 2.2: RP2D Expansion
Cohort B: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.
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Drug: STX-478
STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor. Drug: Fulvestrant Fulvestrant will be administered according to local labeling.
Other Name: Faslodex |
Primary Outcome Measures :
- Part 1.1 (Dose Escalation): Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) [ Time Frame: First 28 days of treatment ]
- Part 1.1 (Dose Escalation): Proportion of participants who experience at least 1 DLT during the first 28 days of treatment. [ Time Frame: First 28 days of treatment ]
- Part 1.1 (Dose Escalation): Cmax of STX-478 [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): AUC(0-inf) of STX-478 [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): AUC(0-t) of STX-478 [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): AUC(0-τ) of STX-478 [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): Change from baseline in ctDNA levels. [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c] [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose. [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide. [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): Objective response rate (ORR). [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): Incidence of TEAEs/SAEs ≥ grade 2. [ Time Frame: 12 months ]
- Part 1.1 (Dose Escalation): Frequency of TEAEs according to CTCAE v5.0 criteria. [ Time Frame: 12 months ]
- RP2D Selection (Parts 1.2-DS and 2.1): Cmax of STX-478 [ Time Frame: 12 months ]
- RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-inf) of STX-478 [ Time Frame: 12 months ]
- RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-t) of STX-478 [ Time Frame: 12 months ]
- RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-τ) of STX-478 [ Time Frame: 12 months ]
- RP2D Selection (Parts 1.2-DS and 2.1): Change from baseline in ctDNA levels. [ Time Frame: 12 months ]
- RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c] [ Time Frame: 12 months ]
- RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose. [ Time Frame: 12 months ]
- RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide [ Time Frame: 12 months ]
- Parts 1.2-DS and 2.1 (RP2D Selection): ORR [ Time Frame: 12 months ]
- Parts 1.2-DS and 2.1 (RP2D Selection): Frequency counts and percentages of AEs based on MedDRA and CTCAE v5.0 [ Time Frame: 12 months ]
- Parts 1.2-DS and 2.1 (RP2D Selection): Proportion of participants with DLTs. [ Time Frame: 12 months ]
- Parts 1.2-DS and 2.1 (RP2D Selection): Change in ECOG performance status. [ Time Frame: 12 months ]
- Parts 1.2-DE, 1.3, and 2.2 (Dose Expansion): ORR defined as the percentage of participants with partial response or complete response based on RECIST 1.1. [ Time Frame: 12 months ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
- Has a new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen within 10 years prior to screening
- Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types) obtained either from tumor or plasma samples, determined by PCR or NGS-based assay as an FDA-approved test in US, CE marked in EU, or obtained as part of normal clinical care in a CLIA certified or similarly certified laboratory.
- Is ≥18 years of age at the time of signing the ICF
- Has an ECOG performance status score of 0 or 1 at screening
Key Exclusion Criteria:
- Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
- Has symptomatic brain or spinal metastases
- Has a tumor with known mutations/deletions in PTEN and activating mutations in AKT (E17K) confirmed by a CLIA-certified or similarly certified laboratory
- Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2 (based on FPG and HbA1c thresholds defined in the inclusion criteria) requiring antihyperglycemic medication
- Cohorts A0, A1, A2, A3, A4, A5 and B: Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
- Has had treatment with any local or systemic antineoplastic therapy or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, prior to the initiation of study treatment up to a maximum washout period of 28 days
- Has toxicities from previous anticancer therapies that have not resolved to baseline levels or CTCAE grade ≤1, with the exception of alopecia and peripheral neuropathy
- Has had radiotherapy within 14 days before the initiation of study treatment
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05768139
Contacts
| Contact: For questions concerning enrollment | Please email: | clinicaltrials@scorpiontx.com |
Locations
Show 26 study locations
Sponsors and Collaborators
Scorpion Therapeutics, Inc.
Investigators
| Study Director: | Mark Chao, MD, PhD | Scorpion Therapeutics, Inc. |
| Responsible Party: | Scorpion Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT05768139 |
| Other Study ID Numbers: |
STX-478-101 2023-000442-41 ( EudraCT Number ) 2023-504807-94-00 ( Other Identifier: EU CT Number ) |
| First Posted: | March 14, 2023 Key Record Dates |
| Last Update Posted: | May 16, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Scorpion Therapeutics, Inc.:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases HER2-negative breast cancer HR-positive breast cancer Gynecologic cancer Endometrial cancer Ovarian cancer Cervical cancer Head and neck cancer Head and neck squamous cell carcinoma Fulvestrant |
Antineoplastic Agents PI3Kα PI3K alpha PI3Kα mutation Alpelisib STX-478 PI3Kα inhibitor Estrogen Receptor Antagonists Estrogen Antagonists Hormone Receptor Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Fulvestrant Antineoplastic Agents, Hormonal |
Antineoplastic Agents Estrogen Receptor Antagonists Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |