PT886 for Stomach Cancer

Recruiting at 10 trial locations

Overseen By Phanes Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Phanes Therapeutics

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Pregnancy, Autoimmune, Pneumonitis, Brain metastases, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

258 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, PT886, on patients with advanced stomach, gastroesophageal, and pancreatic cancers. Researchers aim to see if it is safe and effective by observing its effects on the body and tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you must stop them at least 14 days before starting the study treatment.

What safety information is available for PT886 (CPT-11) in humans?

CPT-11, also known as irinotecan, has been studied in humans for various cancers, including gastric cancer. Major side effects reported include low white blood cell count (leukopenia), low red blood cell count (anemia), diarrhea, and loss of appetite (anorexia), but these were generally reversible. ^{1 2 3 4 5}

Who Is on the Research Team?

Harold Wright, PhD

Principal Investigator

Phanes Therapeutics SrVP of clinical development and operations

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic stomach, gastroesophageal junction, or pancreatic cancers that have no standard treatment options left. Participants must be over 18, able to consent, and meet health criteria like a specific performance status and adequate organ function. They should not be pregnant and agree to use effective contraception.

Inclusion Criteria

My advanced stomach, GEJ, or pancreatic cancer cannot be surgically removed.

My tumor has at least 10% CLDN18.2 positive cells.

I am fully active or can carry out light work.

Exclusion Criteria

I have received an organ or tissue transplant from another person.

I don't have another cancer that's getting worse or was treated in the last 2 years.

I haven't taken steroids or other immune-weakening drugs recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

An accelerated titration design will be employed for early dose levels, followed by the standard 3+3 design at higher dose levels to evaluate safety and determine the recommended dose for expansion.

8-12 weeks

Dose Expansion

Two dose levels will be explored; the recommended dose for expansion (RDE) from Part A, and another dose level to further evaluate safety and efficacy.

12-16 weeks

Combination Expansion

Participants receive Spevatamig (PT886) in combination with either chemotherapy and/or the checkpoint inhibitor pembrolizumab to assess the combination's safety and efficacy.

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PT886

Trial Overview PT886 is being tested in this study; it's a new antibody targeting proteins often found on certain cancer cells which may help the immune system destroy these cells. The trial will check how safe PT886 is, what the body does with it (pharmacokinetics), and if it helps against cancer.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 1 Intervention

Two dose levels will be explored; the recommended dose for expansion (RDE) from Part A, and another dose level.

Group II: Dose Escalation Experimental Treatment 1 Intervention

An accelerated titration design will be employed for early dose levels, followed by the standard 3+3 design at higher dose levels.

Group III: Combination Expansion with KEYTRUDA® (pembrolizumab) Experimental Treatment 6 Interventions

Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab).

Group IV: Combination Expansion with Chemotherapy Experimental Treatment 9 Interventions

Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX.

PT886 is already approved in United States, China for the following indications:

Approved in United States as PT886 for:

• None approved yet; granted Fast Track designation for metastatic claudin 18.2-positive pancreatic adenocarcinoma and orphan drug designation for pancreatic cancer

Approved in China as PT886 for:

• None approved yet; undergoing Phase I clinical trial (CTR20241655)

Who Is Running the Clinical Trial?

Phanes Therapeutics

Lead Sponsor

Trials

3

Recruited

380+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase II study involving 67 patients with metastatic colorectal cancer, CPT-11 demonstrated a partial response rate of 27%, indicating its potential effectiveness even in patients who had previously undergone chemotherapy.

The treatment was generally well tolerated, with manageable side effects such as leukopenia and diarrhea, allowing for outpatient administration without severe toxicity, which suggests a favorable safety profile for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group. Shimada, Y., Yoshino, M., Wakui, A., et al.[2018]

SN38, the active metabolite of CPT-11, rapidly activates the epidermal growth factor receptor (EGFR) in gastric cancer cells, leading to increased production of growth factors and inflammatory cytokines, which may promote tumor growth.

Blocking EGFR activation with gefitinib can prevent the effects induced by SN38, suggesting that combining CPT-11 with gefitinib could enhance treatment efficacy for gastric cancers by targeting EGF signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells. Kishida, O., Miyazaki, Y., Murayama, Y., et al.[2018]

In mouse models of gastrointestinal cancer, intraperitoneal administration of CPT-11 was found to be significantly more effective than intravenous administration in controlling peritoneal seeding and liver metastasis.

This study suggests that using intraperitoneal CPT-11 could be a more efficient method for adjuvant chemotherapy in preventing cancer spread in patients with gastrointestinal malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal versus intravenous CPT-11 for peritoneal seeding and liver metastasis. Maruyama, M., Nagahama, T., Yuasa, Y.[2018]

In a late phase II study involving 81 patients with advanced gastric cancer, irinotecan hydrochloride (CPT-11) demonstrated an overall response rate of 23.3% among evaluable cases, indicating its potential efficacy in this patient population.

The treatment was associated with significant toxicities, including leukopenia (41.2%) and anemia (28.9%), but these were generally reversible, suggesting that while CPT-11 is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group]. Futatsuki, K., Wakui, A., Nakao, I., et al.[2018]

In a review of four randomized controlled trials involving 657 patients with advanced gastric cancer, irinotecan (CPT-11)-containing chemotherapy showed a significant improvement in time to treatment failure (TTF) compared to non-CPT-11 regimens, indicating it may help patients maintain treatment effectiveness longer.

Despite the benefits in TTF, there was no significant difference in overall survival (OS) or overall response rate (ORR) between CPT-11 and non-CPT-11 treatments, and CPT-11 was associated with lower rates of severe hematological and gastrointestinal toxicities, suggesting it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan-involved regimens for advanced gastric cancer: a pooled-analysis of clinical trials. Wang, DL., Gu, DY., Huang, HY., et al.[2021]

Citations

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

Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells. [2018]

3. Greece pubmed.ncbi.nlm.nih.gov

Intraperitoneal versus intravenous CPT-11 for peritoneal seeding and liver metastasis. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

[Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group]. [2018]

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

Irinotecan-involved regimens for advanced gastric cancer: a pooled-analysis of clinical trials. [2021]