Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or Targeted Therapy and/or ICI, for the Treatment of Patients With Advanced Gastrointestinal Cancers, Including Gastric, Gastroesophageal Junction, Pancreatic Ductal or Biliary Tract Carcinomas (the TWINPEAK Study)

Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorPhanes Therapeutics

About this trial

This is a first-in-human, Phase 1/2, open-label, dose escalation and dose expansion and combination study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Spevatamig (PT886). Patients with the following tumor types will be eligible for screening: unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, biliary tract carcinoma (BTC), pancreatic ductal adenocarcinoma (PDAC) and colorectal carcinoma (CRC).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

18 years or older and able to sign informed consent and comply with the protocol.

Measurable disease as defined by RECIST V1.1 criteria for solid tumors.

3. Part A: Histologically or cytologically confirmed unresectable advanced or metastatic solid gastric, gastroesophageal junction (GEJ), biliary tract or pancreatic carcinomas previously treated for advanced (metastatic or unresectable) disease or for which treatment is not available or not tolerated.

Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample (preferably fresh biopsy or if not possible, archival tissue) to be assessed for CLDN18.2 expression and other biomarkers.

Disqualifiers

Women who are pregnant or lactating.

Women of child-bearing potential (WOCBP) who do not use adequate birth control.

Has an active autoimmune disease that has required systemic treatment in the past 2 years.

Prior CLDN18.2 or CD47 targeting therapies, or SIRPα (signal regulatory protein alpha) targeting agents.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Spevatamig (PT886)

    Drug

    Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47.

  • Paclitaxel

    Drug

    Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C1

  • Gemcitabine

    Drug

    Chemotherapy as a combination partner to Abraxane and Spevatamig (PT886) in Part C: substudy C2

  • Abraxane

    Drug

    Chemotherapy as a combination partner to Gemcitabine and Spevatamig (PT886) in Part C: substudy C2

  • KEYTRUDA® (pembrolizumab)

    Drug

    Immune checkpoint inhibitor as a combination partner to Spevatamig (PT886) in Part D.

  • FOLFOX

    Drug

    Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab, Part D only)

  • CAPOX

    Drug

    Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886)

  • FOLFIRINOX

    Drug

    Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3

  • TAS 102

    Drug

    Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudies C5 and C7.

  • Bevacizumab

    Drug

    Targeted therapy as a combination partner to Spevatamig (PT886) in Part C: substudies C6 and C7.

  • Gemcitabine Combined With Cisplatin

    Drug

    Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab) in Part D: substudy D2

  • NALIRIFOX

    Drug

    Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3.

Treatment groups

350 Participants
are divided into 4 treatment groups
Group A: Dose EscalationExperimental treatment 1 intervention
Group B: Dose ExpansionExperimental treatment 1 intervention
Group C: Combination Expansion with Chemotherapy or Targeted TherapyExperimental treatment 9 interventions
Group D: Combination Expansion with KEYTRUDA® (pembrolizumab)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy.

Time frame
Through study completion, an average of 2 years
2

To evaluate anti-tumor activity of PT886 as assessed by ORR, in Spevatamig (PT886) monotherapy and in each combination substudy.

Time frame
Through study completion.
3

To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy.

Time frame
Through study completion.

Secondary outcomes

1

To evaluate the pharmacokinetics of Spevatamig (PT886).

Time frame
Through study completion, an average of 2 years
2

To evaluate the immunogenicity (ADA) of Spevatamig (PT886).

Time frame
Through study completion, an average of 2 years
3

To evaluate anti-tumor activity as assessed by additional measures other than ORR, in Spevatamig (PT886) monotherapy and in each combination substudy.

Time frame
Through study completion, an average of 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Phanes Therapeutics

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator