STX-001 + Keytruda for Solid Tumors

Recruiting at 4 trial locations

Overseen By S Thomas, MSBS

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

Trial Summary

What is the purpose of this trial?

Phase 1/2, Open-label, Multi-center, First-in-human Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of STX-001 Delivered by Intratumoral Injection in Patients with Advanced Solid Tumors as a Monotherapy or in Combination with Pembrolizumab

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.

What data supports the effectiveness of the drug STX-001 + Keytruda for solid tumors?

The study on anlotinib plus PD-1 inhibitors for soft tissue sarcoma suggests that combining drugs with PD-1 inhibitors, like Keytruda, can be effective in treating certain cancers. This implies that using Keytruda with other drugs, such as STX-001, might also be beneficial for solid tumors. ^{1 2 3 4 5}

What safety data exists for STX-001 + Keytruda in humans?

The available research does not provide specific safety data for the combination of STX-001 and Keytruda (Pembrolizumab) in humans. However, Keytruda has been studied in various conditions and is generally considered safe, with known side effects like fatigue, skin reactions, and digestive issues. ^{5 6 7 8 9}

What makes the drug STX-001 + Keytruda unique for treating solid tumors?

STX-001 is a novel fusion protein that targets and neutralizes both VEGF and PlGF, which are involved in tumor blood vessel growth, making it a promising antiangiogenic therapy. When combined with Keytruda, an immunotherapy that blocks PD-1 to help the immune system attack cancer cells, this combination offers a unique approach by simultaneously targeting tumor blood supply and enhancing immune response. ^{10 11 12 13 14}

Research Team

Tasuku Kitada, PhD

Principal Investigator

Strand Therapeutics

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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.

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

A Phase 1, first-in-human (FIH), multiple ascending STX-001 dose administration 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 1m) of STX-001 with new patients enrolled in each dose escalation cohort.

Group III: 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-001 with new patients enrolled in each dose escalation cohort.

Who Is Running the Clinical Trial?

Strand Therapeutics Inc.

Lead Sponsor

Trials

1

Recruited

110+

Findings from Research

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]

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]

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]

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]

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)

pubmed.ncbi.nlm.nih.gov

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]

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]

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]

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]

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]

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)

pubmed.ncbi.nlm.nih.gov

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

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)

pubmed.ncbi.nlm.nih.gov

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of intravenous aflibercept in combination with docetaxel in patients with advanced solid tumors. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Effectiveness and Tolerability of Anlotinib Plus PD-1 Inhibitors for Patients with Previously Treated Metastatic Soft-Tissue Sarcoma. [2022]

3. England 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Phase I Study of AMG 337, a Highly Selective Small-molecule MET Inhibitor, in Patients with Advanced Solid Tumors. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Development and validation of a coding framework to identify severe acute toxicity from systemic anti-cancer therapy using hospital administrative data. [2022]

7. England 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. [2022]

8. United States 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. [2022]

9. United States 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. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

sFLT01: a novel fusion protein with antiangiogenic activity. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

New developments in multitargeted therapy for patients with solid tumours. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]

13. England pubmed.ncbi.nlm.nih.gov

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

14. New Zealand pubmed.ncbi.nlm.nih.gov

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