A Trial to Learn How Safe AZD9750 is and How Well it Works in People With Metastatic Prostate Cancer When Given With or Without Other Anticancer Drugs

Browse trials for

• Prostatic Neoplasms 6,356
• Bulbo-Spinal Atrophy, X-Linked 33

Keywords

• Metastasic Prostate Cancer
• Prostate Cancer
• Androgen Receptor
• Proteolysis-targeting chimeras (PROTACs)

Study arms

• Experimental
  Module 1 / Part A1

  AZD9750 Monotherapy (Dose Escalation) - No randomization

  Drug: AZD9750

• Experimental
  Module 1 / Part A2

  AZD9750 Monotherapy (Backfills) - No randomization

  Drug: AZD9750

• Experimental
  Module 1 / Part B1

  AZD9750 Monotherapy (Dose Optimization) - Randomization

  Drug: AZD9750

• Experimental
  Module 1 Part B2

  AZD9750 Monotherapy (Dose Expansion) - No randomization

  Drug: AZD9750

• Experimental
  Module 1 / Part B3

  AZD9750 Monotherapy (Dose Expansion) - No randomization

  Drug: AZD9750

• Experimental
  Module 2 / Part A

  AZD9750 + Saruparib (Combination Dose Finding) - No Randomization

  Drug: AZD9750 · Drug: AZD5305

• Experimental
  Module 2/ Part B

  AZD9750 + Saruparib (Combination Dose Expansion) - No Randomization

  Drug: AZD9750 · Drug: AZD5305

Interventions

• DrugAZD9750

  AR-PROTAC

• DrugAZD5305

  PARP1-selective inhibitor

  Also known as: Saruparib

Primary outcomes

1. Number of participants with dose-limiting toxicity (DLT), as defined in the protocol (Part A only)

   To evaluate the safety and tolerability and determine the MTD and/or the RDE(s)/RP2D of AZD9750 as a monotherapy and in combination with other anticancer agents in participants with mCRPC. A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness.

   Time frame: From first dose of study intervention to 28 days post first dose

2. Number of participants with Adverse Events and Serious Adverse Events

   The number of participants with adverse events and with serious adverse events will be assessed.

   Time frame: From first dose of study intervention up to 37 days after the last dose of study treatment

3. Number of participants with Adverse Events leading to discontinuation of study intervention

   The number of participants with clinically significant changes from baseline in vital signs will be assessed.

   Time frame: From first dose of study intervention up to 37 days after the last dose of study treatment

4. Clinically significant changes from baseline in vital signs.

   The number of participants with clinically significant changes from baseline in vital signs will be assessed.

   Time frame: From first study dose up to 37 days after the last dose of study treatment

5. Clinically significant changes from baseline in physical examination.

   The number of participants with clinically significant changes from baseline in physical examination will be assessed.

   Time frame: From first dose of study intervention up to 37 days after the last dose of study treatment

6. Clinically significant changes from baseline in ECOG PS.

   The number of participants with clinically significant changes from baseline in ECOG PS will be assessed.

   Time frame: From first dose of study intervention up to 37 days after the last dose of study treatment

7. Clinically significant changes from baseline in ECGs.

   The number of participants with clinically significant changes from baseline in ECGs will be assessed.

   Time frame: From first dose of study intervention up to 37 days after the last dose of study treatment

8. Clinically significant changes from baseline in laboratory parameters.

   The number of participants with clinically significant changes from baseline in laboratory parameters will be assessed.

   Time frame: From first dose of study intervention up to 37 days after the last dose of study treatment

9. Proportion of participants achieving a ≥50% decrease in PSA from baseline (PSA50) (Part B only)

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents in participants with mCRPC.

   Time frame: From first dose of study intervention up to 14 days after the last dose of study treatment

Secondary outcomes

1. Proportion of participants achieving a ≥ 50% decrease in PSA from baseline (PSA50) (Part A only)

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents.

   Time frame: From first dose of study intervention up to initiation of subsequent anticancer therapy (or radiotherapy on target lesions), PSA progression or 14 days after the last dose of study treatment

2. Proportion of participants achieving a ≥ 90% decrease in PSA from baseline (PSA90)

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents.

   Time frame: From first dose of study intervention up to initiation of subsequent anticancer therapy (or radiotherapy on target lesions), PSA progression or 14 days after the last dose of study treatment

3. Objective response rate (ORR)

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents. ORR will be assessed according to RECIST v1.1 and PCWG3 criteria (bone) and is defined as the percentage of participants who have a confirmed best overall response of CR or PR or NED (in case the subject has neither TLs nor NTLs at baseline) that occurs prior to the initiation of subsequent anticancer treatment (or radiotherapy on target lesions) and prior to progression.

   Time frame: From randomisation or first dose of study intervention to initiation of subsequent anticancer treatment (or radiotherapy on target lesions) or progression, assessed up to 60 months

4. Duration of response (DoR)

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents. DoR is defined as the time from the date of first documented objective response (which is subsequently confirmed) until the date of first documented radiological disease progression or death (by any cause in the absence of disease progression).

   Time frame: From randomisation or first dose of study intervention to the date of first documented radiological disease progression, assessed up to 60 months

5. Time to response (TTR)

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents. TTR is defined as the time from randomisation/first dose until the first documentation of a subsequently confirmed objective response prior to progression and prior to starting any subsequent cancer therapy (or radiotherapy on target lesions).

   Time frame: From randomisation or first dose of study intervention to initiation of subsequent anticancer treatment (or radiotherapy on target lesions) or progression, assessed up to 60 months

6. Radiographic progression-free survival (rPFS)

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents. rPFS is defined as the time from the date of randomisation or first dose until the date of radiographic progression, as assessed per RECIST v1.1 (soft tissue) and/or PCWG3 criteria (bone) and derived from the raw tumour data or death (by any cause in the absence of progression).

   Time frame: From randomisation or first dose of study intervention to progression, assessed up to 60 months

7. Best percentage change in target lesion size from baseline

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents. The best change in tumour size from baseline (i.e. depth of response) is the largest decrease from baseline or the smallest increase from baseline in the absence of a reduction and includes all assessments: * up to and including the first visit at which the overall visit response is PD, * prior to death in the absence of progression, * prior to the start of subsequent anti-cancer therapy (or radiotherapy on target lesions) * or up to and including the last evaluable RECIST assessment if the subject has not died, progressed or started subsequent anti-cancer therapy (or radiotherapy on target lesions).

   Time frame: From screening (Day -28) to initiation of subsequent anticancer treatment (or radiotherapy on target lesions) or progression, assessed up to 60 months

8. Time to PSA response (TTPSA50, TTPSA90)

   To evaluate the preliminary antitumour efficacy of AZD9750 as monotherapy and in combination with other anticancer agents. TTPSA is defined as the time from randomisation or first dose date until the date of the first documented PSA50 or PSA90 response (which is subsequently confirmed), respectively.

   Time frame: From first dose of study intervention up to initiation of subsequent anticancer therapy (or radiotherapy on target lesions), PSA progression or 14 days after the last dose of study treatment

9. Cmax of AZD9750

   To characterize the PK of AZD9750 as monotherapy and in combination with other anticancer agents.

   Time frame: From date of first dose of study intervention up to 115 days after first dose

10. tmax of AZD9750

    To characterize the PK of AZD9750 as monotherapy and in combination with other anticancer agents.

    Time frame: From date of first dose of study intervention up to 115 days after first dose

11. AUC of AZD9750

    To characterize the PK of AZD9750 as monotherapy and in combination with other anticancer agents.

    Time frame: From date of first dose of study intervention up to 115 days after first dose

12. Cmax of saruparib (Module 2 only)

    To characterize the PK of saruparib in combination with AZD9750.

    Time frame: From date of first dose of study intervention up to 57 days after first dose

13. Tmax of saruarib (Module 2 only)

    To characterize the PK of saruparib in combination with AZD9750.

    Time frame: From date of first dose of study intervention up to 57 days after first dose

14. AUC of saruparib (Module 2 only)

    To characterize the PK of saruparib in combination with AZD9750.

    Time frame: From date of first dose of study intervention up to 57 days after first dose