STX-001 + Keytruda for Solid Tumors

Recruiting at 7 trial locations

Overseen By S Thomas, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Strand Therapeutics Inc.

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Autoimmune disease, Organ transplant, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of a new treatment, STX-001, for individuals with advanced solid tumors, either alone or in combination with Keytruda, an immunotherapy drug. Researchers seek to understand how the treatment functions in the body and its potential to shrink tumors. Individuals with advanced cancer who have not responded to other treatments may be suitable candidates, particularly those with tumors that can be directly injected. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, providing participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot use another anticancer therapy within 3 weeks before starting the trial, and active use of systemic anticoagulants is not allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found STX-001 to be safe when used alone in people with advanced solid tumors. Most participants tolerated the treatment well, and no serious side effects occurred, indicating a positive safety profile.

Researchers also tested STX-001 with Keytruda (pembrolizumab) to assess whether the combination could enhance the immune system's ability to fight cancer. Although specific details about side effects are unavailable, the treatments were closely monitored for safety issues. This careful observation suggests researchers have enough confidence in the safety to continue testing.

As a Phase 1/2 trial, the primary goal is to gather more information about safety. Early trials like this often focus on determining a safe dose and identifying any unwanted side effects. The trial's progression indicates the treatment is considered safe enough for further study. If major safety problems had arisen, the trial would likely have been stopped or modified. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care, which often includes chemotherapy, radiation, and surgery for solid tumors, STX-001 acts on tumors in a novel way. STX-001 is administered intratumorally, directly targeting cancer cells, which may enhance effectiveness while potentially reducing systemic side effects. When combined with pembrolizumab, an immune checkpoint inhibitor, it might boost the body's immune response against cancer cells more effectively. Researchers are excited about its ability to work synergistically with pembrolizumab, targeting tumor cells and potentially improving outcomes for patients with advanced cancers like triple-negative breast cancer and melanoma.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that STX-001, used alone or with pembrolizumab (Keytruda®), may help treat solid tumors. In this trial, some participants will receive STX-001 as a monotherapy, while others will receive it combined with pembrolizumab. STX-001 is a new treatment that instructs cells to enhance the body's immune response against cancer. Early studies have demonstrated that this can help the immune system recognize and kill cancer cells. Pembrolizumab is already known for aiding the immune system in fighting cancer and has been effective in treating cancers like melanoma and lung cancer. When used together, early evidence suggests that STX-001 and pembrolizumab may effectively shrink tumors in difficult-to-treat cases. While research is ongoing, these treatments have shown promising results in early trials. ^{1 2 3 4 5}

Who Is on the Research Team?

Jason Luke, MD

Principal Investigator

Strand Therapeutics

Are You a Good Fit for This Trial?

This trial is for individuals with advanced solid tumors. Participants should be adults who have tried other treatments that didn't work or aren't suitable. They must be able to receive injections directly into their tumor and can handle biopsies. People with immune system disorders, certain blood conditions, or those on steroids may not qualify.

Inclusion Criteria

My TNBC can't be cured with surgery or radiation, and I've had specific prior treatments.

It has been over 4 weeks since my last major surgery.

Willing and able to provide blood samples prior to the start of this study

Exclusion Criteria

I haven't had uncontrolled bleeding or a bleeding disorder in the last week.

I have previously received IL-12 therapy.

Previously enrolled in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Multiple ascending dose and dose expansion study of STX-001 as monotherapy or in combination with pembrolizumab to evaluate safety, tolerability, PK, PD, and preliminary antitumor activity

Varies by cohort

Phase 2 Treatment

Dose expansion cohorts in patients with triple-negative breast cancer and melanoma to evaluate STX-001 in combination with pembrolizumab

Varies by cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• STX-001

Trial Overview The study tests STX-001 as a solo treatment and combined with Pembrolizumab (Keytruda®), an existing cancer drug. It's given by injection straight into the tumor to see how safe it is, how the body reacts to it, and if it helps against the cancer.

How Is the Trial Designed?

Group I: Phase 2 Combination (STX-001 with Pembrolizumab) Experimental Treatment 2 Interventions

Phase 2 consists of dose expansion cohorts in patients with 2 defined cancer types: triple negative breast cancer (TNBC) and melanoma. Phase 2 will evaluate STX-001 in combination with pembrolizumab; the recommended Phase 2 dose (RP2D) of STX-001 will be selected based on analysis of the totality of data from Phase 1 safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy data. Dose extension and treatment pauses are incorporated.

Group II: Phase 2 Advanced-Melanoma Monotherapy Experimental Treatment 1 Intervention

Phase 2 dose expansion cohort evaluating STX-001 monotherapy administered intratumorally to patients with advanced melanoma. Assesses safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity with the recommended dose selected based on Phase 1 data. Dose extension and treatment pauses are allowed up to 35 cycles.

Group III: Phase 1 Visceral-lesion Monotherapy (Cohort 1Vm) Experimental Treatment 1 Intervention

Phase 1, first-in-human (FIH) monotherapy cohort targeting visceral lesions. STX-001 is administered intratumorally at 30 µg, 100 µg and 300 µg to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity in patients with advanced cancers. Cohort 1Vm is part of the dose escalation stage; new patients are enrolled at each dose level, and backfill enrollment is permitted up to 30 patients. Dose escalation may be stopped early if PK or safety data warrant it.

Group IV: Phase 1 Monotherapy (STX-001) Experimental Treatment 1 Intervention

A Phase 1, first-in-human (FIH), multiple ascending dose administration of intratumoral STX-001 monotherapy to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity in patients with advanced cancers. Consists of four planned dose-escalation cohorts (Cohorts 1m) plus permitted backfill enrollment (up to 30 patients). New patients are enrolled in each dose escalation cohort, and dose escalation may be stopped early if emerging PK or safety data warrant it. Dose extension and treatment pauses are integrated, with a maximum extension of 35 cycles (≈24 months).

Group V: Phase 1 Combination (STX-001 with Pembrolizumab) Experimental Treatment 2 Interventions

A Phase 1, first-in-human (FIH), multiple ascending STX-001 dose administration, in combination with pembrolizumab, to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity in patients with advanced cancers. Consists of 4 planned dose escalation cohorts (Cohorts 1c) of STX-001and pembrolizumab given concurrently, with new patients enrolled in each dose escalation cohort. Dose escalation may be halted early if PK or safety data indicate, and the dose extension period extends up to 35 cycles with treatment pauses. Backfill enrollment is permitted up to 30 patients.

Who Is Running the Clinical Trial?

Strand Therapeutics Inc.

Lead Sponsor

Trials

1

Recruited

110+

Published Research Related to This Trial

The maximum tolerated dose (MTD) of sunitinib when combined with pemetrexed and carboplatin for patients with advanced solid tumors was determined to be 37.5 mg/day on a 2 weeks on, 1 week off schedule, with significant safety concerns including high rates of neutropenia and thrombocytopenia.

At the established MTD, 60% of evaluable patients with non-small cell lung cancer or mesothelioma experienced stable disease for at least 8 weeks, indicating some efficacy of the treatment combination despite the need for dose adjustments due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignancies--results of a phase I dose-escalation study. Blais, N., Camidge, DR., Jonker, DJ., et al.[2022]

sFLT01 is a novel fusion protein that effectively inhibits tumor growth and angiogenesis in various preclinical cancer models, demonstrating significant antitumor activity against multiple types of cancer, including lung, colon, and renal cell carcinomas.

In combination with cyclophosphamide, sFLT01 enhances tumor growth inhibition compared to either treatment alone, indicating its potential as a next-generation antiangiogenic therapy that targets both VEGF and PlGF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

sFLT01: a novel fusion protein with antiangiogenic activity. Bagley, RG., Kurtzberg, L., Weber, W., et al.[2020]

Testicular germ cell tumors (GCTs) are the most common cancer in young males aged 15 to 35, with a high overall cure rate of about 95%, but a significant risk of death (25%) in patients with distant metastases.

The case study reports the use of pembrolizumab, a PD-L1 inhibitor, in a phase II trial for a patient with metastatic GCTs who had not responded to multiple chemotherapy treatments, suggesting potential for immunotherapy in treating resistant cases.

NCBI (Pubmed)

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Novel Therapies in Platinum-refractory Metastatic Germ Cell Tumor: A Case Report with a Focus on a PD-1 Inhibitor. Loh, KP., Fung, C.[2020]

Targeted therapies, including monoclonal antibodies and small-molecule inhibitors, are showing promise in treating solid tumors by selectively attacking cancer pathways while minimizing adverse effects, thus maintaining patients' quality of life.

Current research is expanding the use of these therapies beyond established cancers like colorectal and breast cancer to include ongoing trials for various other tumor types, highlighting the evolving landscape of cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies for solid tumors: current status and future perspectives. Stoffel, A.[2018]

In a study of 32 patients with previously treated metastatic soft tissue sarcoma, the combination of anlotinib and PD-1 inhibitors showed a promising objective response rate of 34.4% and a disease control rate of 84.4%, indicating effective treatment outcomes.

The treatment was generally well-tolerated, with 90.6% of patients experiencing adverse reactions, mostly mild to moderate, and no grade 5 adverse reactions reported, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Tolerability of Anlotinib Plus PD-1 Inhibitors for Patients with Previously Treated Metastatic Soft-Tissue Sarcoma. Sun, X., Xu, J., Xie, L., et al.[2022]

In a phase I study involving 54 patients with advanced solid tumors, aflibercept combined with docetaxel showed a recommended phase II trial dose of 6 mg/kg, with manageable dose-limiting toxicities including neutropenic infection and hypertension.

The combination treatment resulted in partial responses in 7 patients and stable disease in 32 patients, indicating potential efficacy in this patient population despite significant adverse events like neutropenia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of intravenous aflibercept in combination with docetaxel in patients with advanced solid tumors. Isambert, N., Freyer, G., Zanetta, S., et al.[2018]

The combination of CXD101 and nivolumab was well tolerated in patients with microsatellite stable metastatic colorectal carcinoma, with manageable side effects such as neutropenia (18%) and anemia (7%), and no treatment-related deaths reported.

In terms of efficacy, 48% of patients achieved either a partial response or stable disease, with a median overall survival of 7.0 months, indicating that this combination therapy may provide a beneficial treatment option for heavily pre-treated patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CXD101 and nivolumab in patients with metastatic microsatellite-stable colorectal cancer (CAROSELL): a multicentre, open-label, single-arm, phase II trial. Saunders, MP., Graham, J., Cunningham, D., et al.[2023]

In a study of 105 soft-tissue sarcoma (STS) cases, 65% showed infiltration of PD1-positive lymphocytes and 58% exhibited PD-L1 expression, both of which were linked to more advanced disease and poorer outcomes.

Both PD1 and PD-L1 positivity were identified as independent prognostic indicators for overall survival and event-free survival in STS, suggesting that these markers could help select patients for PD1-targeted immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas. Kim, JR., Moon, YJ., Kwon, KS., et al.[2022]

Lenvatinib plus pembrolizumab had the highest rates of severe treatment-related adverse events (grade ≥3 TRAEs) and treatment discontinuation among the combination therapies for advanced renal cell carcinoma.

Nivolumab plus ipilimumab had the lowest rates of severe TRAEs but was linked to more endocrine-related adverse events, highlighting the need to balance efficacy with safety in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of systemic immune-based combination therapies in the first-line treatment of patients with metastatic renal cell carcinoma: systematic review and network meta-analysis. Quhal, F., Mori, K., Remzi, M., et al.[2023]

A new coding framework was developed and validated to identify severe acute toxicities in colon cancer patients treated with systemic anti-cancer therapy (SACT), showing a 26.4% toxicity rate in adjuvant therapy and 53.4% in metastatic cases.

The framework revealed that specific SACT regimens, such as those including bevacizumab, were associated with higher rates of severe toxicities like bleeding and gastrointestinal issues, highlighting the importance of monitoring these effects in real-world settings.

NCBI (Pubmed)

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Development and validation of a coding framework to identify severe acute toxicity from systemic anti-cancer therapy using hospital administrative data. Boyle, JM., Cowling, TE., Kuryba, A., et al.[2022]

AMG 337, an oral MET inhibitor, was found to be tolerable with manageable side effects, establishing a maximum tolerated dose of 300 mg once daily in a study involving 111 patients with advanced solid tumors.

The treatment showed a promising objective response rate of 29.6% in patients with MET-amplified tumors, suggesting potential efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors. Hong, DS., LoRusso, P., Hamid, O., et al.[2023]

In a study of 470 Japanese patients with imatinib-resistant or intolerant gastrointestinal stromal tumors, sunitinib demonstrated good efficacy with a 20% objective response rate and a median progression-free survival of 22.4 weeks.

The treatment was generally well-tolerated, with 70% of patients experiencing grade ≥ 3 adverse events, but specific early adverse events like hand-foot syndrome and leukopenia were linked to improved progression-free survival, indicating they may serve as positive prognostic markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor. Komatsu, Y., Ohki, E., Ueno, N., et al.[2022]

Molecularly targeted anticancer therapies, such as imatinib, sunitinib, sorafenib, and dasatinib, have shown significant advances in treating specific solid tumors and exhibit potential effectiveness in other tumor types based on phase II/III clinical data.

Emerging multitargeted agents are showing promise in early phase trials across various tumor types, but further research is needed to confirm their clinical relevance and to optimize treatment strategies for patient populations that would benefit the most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in multitargeted therapy for patients with solid tumours. Le Tourneau, C., Faivre, S., Raymond, E.[2018]

Targeted and immunological therapies have significantly improved survival rates in patients with solid tumors, demonstrating the effectiveness of treatments that focus on specific genetic and immunological changes in tumors.

Current clinical trials are exploring the optimal timing and sequencing of these therapies, which include various approved agents for cancers like prostate, breast, lung, and melanoma, indicating a shift towards more personalized cancer treatment strategies.

NCBI (Pubmed)

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[Pharmacotherapy of solid tumors. New hopes and frustrations]. Grünwald, V., Rickmann, M.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06249048

NCT06249048 | Phase 1/2 Study of Intratumoral Injection ... A Phase 1, first-in-human (FIH), multiple ascending dose administration of intratumoral STX-001 monotherapy to evaluate safety, tolerability, pharmacokinetics ( ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9556

Phase I dose escalation trial of STX-001, an LNP ... STX-001 is a lipid nanoparticle-encapsulated self-replicating mRNA that activates innate immunity, promotes immunogenic cancer cell death, and expresses IL-12 ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03569

Phase 1/2 Study of Intratumoral Injection of STX-001 in ... Phase 1/2, Open-label, Multi-center, First-in-human Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of STX-001

4. trials.cancervic.org.au trials.cancervic.org.au/details/vctl_nct06249048

STRAND STX-001-01 - Victorian Cancer Trials Link This study is assessing how safe, tolerable and effective a new drug (called STX-001) is on its own and in combination with a standard ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2696

A phase I trial of intratumoral STX-001: A novel self- ... This Phase 1 open-label, multi-center first-in-human dose-escalation trial evaluates the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD),