A Study of PHST001 in Advanced Solid Tumors

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• Ovarian Neoplasms 2,695
• Endometrial Neoplasms 1,325
• Cholangiocarcinoma 914
• Central Nervous System Neoplasms 673
• Breast Neoplasms 12,544
• Fallopian Tube Neoplasms 720

Ovarian Neoplasms

2,695 studies on the registry are indexed under Ovarian Neoplasms; 727 are open to participants now.

This study's planned enrollment of 426 is above the median of 60 across 2,030 interventional studies indexed under Ovarian Neoplasms.

Lead sponsor

This is the only study on the registry with Pheast Therapeutics as lead sponsor.

Eligibility criteria

Study arms

• Experimental
  PHST001 Monotherapy

  Participants will receive PHST001 monotherapy administered once every 3 weeks (Q3W). In Phase 1a, PHST001 will be evaluated in sequential dose-escalation cohorts at planned dose levels of 0.1, 0.3, 1.0, 2.0, 4.0, 6.0, 9.0, 18.0, and 36.0 mg/kg. Dose levels may be modified or additional dose levels evaluated based on emerging safety, pharmacokinetic, pharmacodynamic, and antitumor activity data. Participants in the Phase 1b biomarker cohort may also receive PHST001 monotherapy.

  Biological: PHST001

• Experimental
  PHST001 + Paclitaxel

  Participants will receive PHST001 in combination with paclitaxel. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in tumor-specific expansion cohorts, including participants with ovarian carcinoma, endometrial carcinoma, or cholangiocarcinoma, and/or in the biomarker cohort.

  Biological: PHST001 · Drug: Paclitaxel

• Experimental
  PHST001 + Topotecan

  Participants will receive PHST001 in combination with topotecan. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in the ovarian carcinoma expansion cohort and/or biomarker cohort.

  Biological: PHST001 · Drug: Topotecan

• Experimental
  PHST001 + Doxorubicin

  Participants will receive PHST001 in combination with doxorubicin. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in ovarian carcinoma or endometrial carcinoma expansion cohorts and/or the biomarker cohort.

  Biological: PHST001 · Drug: Doxorubicin

• Experimental
  PHST001 + FOLFIRI

  Participants will receive PHST001 in combination with FOLFIRI (5-fluorouracil, folinic acid, and irinotecan). The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in the cholangiocarcinoma expansion cohort and/or biomarker cohort.

  Biological: PHST001 · Drug: FOLFIRI

• Experimental
  PHST001 + FOLFOX

  Participants will receive PHST001 in combination with FOLFOX (5-fluorouracil, folinic acid, and oxaliplatin). The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in the cholangiocarcinoma expansion cohort and/or biomarker cohort.

  Biological: PHST001 · Drug: FOLFOX

• Experimental
  PHST001 + Gemcitabine

  Participants will receive PHST001 in combination with gemcitabine. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in ovarian carcinoma or cholangiocarcinoma expansion cohorts and/or the biomarker cohort.

  Biological: PHST001 · Drug: Gemcitabine

• Experimental
  PHST001 + Mirvetuximab Soravtansine

  Participants will receive PHST001 in combination with mirvetuximab soravtansine. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in the ovarian carcinoma expansion cohort and/or in the biomarker cohort. Half of the participants in the randomized ovarian carcinoma cohort may be randomly assigned to receive PHST001 in combination with mirvetuximab soravtansine.

  Biological: PHST001 · Biological: Mirvetuximab Soravtansine

• Experimental
  PHST001 + Trastuzumab Deruxtecan

  Participants will receive PHST001 in combination with trastuzumab deruxtecan. The combination will initially be evaluated in a Phase 1b safety run-in group. Following safety clearance, the combination may be evaluated in participants with advanced or metastatic breast cancer and/or in the biomarker cohort.

  Biological: PHST001 · Biological: Trastuzumab Deruxtecan

• Active comparator
  Mirvetuximab Soravtansine Monotherapy

  Participants with ovarian carcinoma enrolled in the randomized Phase 1b expansion cohort will be randomized 1:1 to receive mirvetuximab soravtansine monotherapy or mirvetuximab soravtansine in combination with PHST001. Participants assigned to this arm will receive mirvetuximab soravtansine monotherapy.

  Biological: Mirvetuximab Soravtansine

Interventions

• BiologicalPHST001

  PHST001 is an anti-CD24 macrophage checkpoint inhibitor, administered as IV infusions every 3-weeks (Q3W) dosing intervals.

• DrugPaclitaxel

  Paclitaxel used as per standard of care.

  Also known as: Taxol

• DrugTopotecan

  Topotecan used as per standard of care.

  Also known as: Hycamtin

• DrugDoxorubicin

  Doxorubicin used as per standard of care.

  Also known as: Adriamycin

• DrugFOLFIRI

  FOLFIRI used as per standard of care.

  Also known as: folinic acid (leucovorin), fluorouracil (5-FU), and irinotecan combination

• DrugFOLFOX

  FOLFOX used as per standard of care.

  Also known as: folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin combination

• DrugGemcitabine

  Gemcitabine used as per standard of care.

  Also known as: Gemzar

• BiologicalMirvetuximab Soravtansine

  Mirvetuximab soravtansine used as per standard of care.

  Also known as: MIRV, Elahere

• BiologicalTrastuzumab Deruxtecan

  Trastuzumab deruxtecan used as per standard of care.

  Also known as: T-DXd, Enhertu

Primary outcomes

1. Frequency of Dose-Limiting Toxicities (DLTs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Based on toxicities observed

   Time frame: From first dose of PHST001 through 21 days after the first dose of PHST001

2. Frequency of Serious Adverse Events (SAEs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Based on toxicities observed

   Time frame: From signed consent up to 90 days after the last dose of PHST001

3. Frequency of Treatment Emergent Adverse Events (TEAEs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Based on toxicities observed

   Time frame: From first dose up to 90 days after the last dose of PHST001

4. Frequency of Treatment Related Adverse Events (TRAEs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Based on toxicities observed

   Time frame: From first dose up to 90 days after the last dose of PHST001

5. Frequency of Adverse Events of Special Interest (AESIs) to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Based on toxicities observed

   Time frame: From first dose up to 90 days after the last dose of PHST001

6. Frequency of AEs Leading to Dose Interruption or Treatment Discontinuation and AEs Leading to Death to assess the safety and tolerability of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Based on toxicities observed

   Time frame: From first dose up to 90 days after the last dose of PHST001

7. Overall Response Rate (ORR) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with anticancer therapy (Phase 1b non-randomized cohorts only)

   Defined as the proportion of subjects with confirmed complete response (CR) or partial response (PR); a confirmed response is a response that persists on repeat-imaging ≥ 4 weeks after initial documentation of response.

   Time frame: From screening and during treatment up to 2 years

8. Progression-Free Survival (PFS) based on RECIST v1.1 to assess the preliminary antitumor activity of PHST001 in combination with anticancer therapy (Phase 1b randomized cohort only)

   Defined as the time from first dose of PHST001 to first documentation of radiographic disease progression or death, whichever occurs first.

   Time frame: From screening and during treatment up to 2 years

Secondary outcomes

1. Overall Response Rate (ORR) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a) and in combination with anticancer therapy (Phase 1b - randomized cohort only)

   Defined as the proportion of subjects with confirmed complete response (CR) or partial response (PR); a confirmed response is a response that persists on repeat-imaging ≥ 4 weeks after initial documentation of response.

   Time frame: From screening and during treatment up to 2 years

2. Duration of Response (DOR) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a) and in combination with anticancer therapy (Phase 1b)

   Defined as time from date of first objective response (either CR or PR) to first documentation of radiographic disease progression.

   Time frame: From screening and during treatment up to 2 years

3. Best Overall Response (BOR) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a) and in combination with anticancer therapy (Phase 1b)

   Defined as the best response recorded for a participant across all time-point assessments from the start of treatment until disease progression or end of treatment.

   Time frame: From screening and during treatment up to 2 years

4. Progression-Free Survival (PFS) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a) and in combination with anticancer therapy (Phase 1b - non-randomized cohorts only) .

   Defined as the time from first dose of PHST001 to first documentation of radiographic disease progression or death, whichever occurs first.

   Time frame: From screening and during treatment up to 2 years

5. Overall Survival (OS) based on RECIST v1.1 (or RANO for primary CNS Tumors) to assess the preliminary antitumor activity of PHST001 as monotherapy (Phase 1a) and in combination with anticancer therapy (Phase 1b).

   Defined as the time from first dose of PHST001 to the date of death.

   Time frame: From screening and during treatment up to 2 years

6. Maximum Observed Concentration (Cmax) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b).

   Defined as the maximum blood concentration of a dose of PHST001

   Time frame: From treatment until 90 days after last dose of PHST001

7. Time to Maximum Concentration (tmax) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Defined as the time required for a dose of PHST001 to reach its maximum blood concentration (Cmax) after administration.

   Time frame: From treatment until 90 days after last dose of PHST001

8. Concentration at the End of a Dosing Interval (Ctrough) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Defined as the blood concentration of a dose of PHST001 at the end of the dosing interval (just prior to next drug administration).

   Time frame: From treatment until 90 days after last dose of PHST001

9. Area Under the Concentration-time Curve (AUC) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

   Defined as the total PHST001 exposure over time, calculated as the integral of the plasma concentration-time profile.

   Time frame: From treatment until 90 days after last dose of PHST001

10. Volume of Distribution at Steady-state (Vss) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

    Defined as how widely PHST001 spreads throughout the body once things have stabilized after a dose has been administered.

    Time frame: From treatment until 90 days after last dose of PHST001

11. Clearance (CL) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

    Defined as the rate at which the body "cleans out" a dose of PHST001 from the bloodstream.

    Time frame: From treatment until 90 days after last dose of PHST001

12. Terminal Elimination Half-life (t½) to characterize the serum PK of PHST001 as monotherapy (Phase 1a) or in combination with anticancer therapy (Phase 1b)

    Defined as the time it takes for the amount of PHST001 in the body to drop by half during the final phase of elimination.

    Time frame: From treatment until 90 days after last dose of PHST001